MRI coronal views from two sets of monozygotic twins discordant for schizophrenia showing subtle enlargement of the lateral ventricles in the affected twins (panels B and D) as compared with the unaffected twins (panels A and C), even when the affected twin had small ventricles.

Magnetic resonance imaging (MRI) is a critical tool for translational neuroscience, but preclinical studies frequently rely on anesthesia, which alters neural activity and limits comparison with human studies. Awake rodent functional MRI (fMRI) enables investigation of brain function under physiologically relevant conditions; however, its implementation is constrained by the need for anesthesia during restraint setup. We developed and evaluated a restraint system and habituation protocol for awake rat fMRI. Ten rats were studied: an awake group and an anesthetized group (three males and two females per group). The protocol included head post implantation and an 11 d habituation period. T2-weighted anatomical and functional scans were acquired. Head motion and functional connectivity were analyzed using the RABIES pipeline and compared between groups. The modular 3D-printed restraint system developed can be assembled in under 5 min; eliminates the need for anesthesia, ear bars, and bite bars; and supports s...

The ability to stop motor responses depends critically on the right inferior frontal cortex (IFC) and also engages a midbrain region consistent with the subthalamic nucleus (STN). Here we used diffusion-weighted imaging (DWI) tractography to show that the IFC and the STN region are connected via a white matter tract, which could underlie a “hyperdirect” pathway for basal ganglia control. Using a novel method of “triangulation” analysis of tractography data, we also found that both the IFC and the STN region are connected with the presupplementary motor area (preSMA). We hypothesized that the preSMA could play a conflict detection/resolution role within a network between the preSMA, the IFC, and the STN region. A second experiment tested this idea with functional magnetic resonance imaging (fMRI) using a conditional stop-signal paradigm, enabling examination of behavioral and neural signatures of conflict-induced slowing. The preSMA, IFC, and STN region were significantly activated the greater the conflict-...

We developed and implemented Functional MRI (fMRI) method, capable of delivering high-resolution definition of regionally specific brain activities as real-time biofeedback signal. We postulated that the feedback of brain function (i.e. neurofeedback) would assist subjects to achieve significant degree of modulation in the primary and secondary auditory areas by adjusting the level of attention to the incoming auditory stimuli. The experiment was conducted at high-field (3 Tesla) MR system, with near real-time fMRI data processing and anatomical segmentation capability. Five healthy volunteers participated in the fMRI examination, which consisted of six baseline scan sessions (three pre- and three post-neurofeedback trials) and five neurofeedback trial sessions. A reference scan session was conducted to delineate the target modulatory areas in the transverse temporal gyrus. In each fMRI session, auditory stimuli (computer generated 850Hz tone with +/- 30% bandwidth frequency modulation at 4Hz oscillation) ...

Rectus pulleys are predicted to shift in convergence (Clark et al, IOVS 41:3787, 2000). Tri-planar gadodiamide contrast MRI was obtained in 8 young adults during binocular fixation of a target aligned to one eye at 800 and 15 cm distance. EOM cross sections and paths were determined from area centroids. In convergence, the aligned eye rotated 0.3±0.6° (mean±SE) horizontally and 0.6±0.6° vertically with 0.6±0.1 mm lens thickening. The aligned globe moved anteriorly 0.2±0.5 mm. Focal cross section increases occurred with convergence in the aligned eye medial rectus (MR), lateral rectus (LR), and inferior oblique (IO), the latter increasing by 1.5±0.4 sq mm (P<0.05). The converging eye rotated nasally 22.4±0.8° and superiorly 0.5±0.5°, with 0.5±0.1 mm lens thickening. The converging globe moved anteriorly 0.2±0.5 mm. Interocular spacing decreased by 0.6±0.3 mm (P<0.05). The converging eye MR and LR had large contractile cross section changes, but IO also increased by 1.8±0.5 sq mm (P<0.05). Anterior paths of ...

Speech production requires the precise timing of around 100 muscles involved in articulation. The neural basis of the exact coordination of these movements is not entirely clear. Here we investigated brain activation associated with overt sub-lexical articulations using event-related fMRI with compressed image acquisition. Nine young healthy volunteers (right-handed, fluent speakers of English; 5 men) were included. Subjects were asked to repeat acoustically presented speech sounds of different complexity and to perform non-verbal oral movements. The required responses were the vowel /a/, a consonant-vowel (CV) syllable (either /pa/, /ka/, or /ta/), a three-syllabic utterance (/pataka/), and oral movements (opening the mouth or protruding the lips). All instructions were delivered and all responses were made within the silent interval between the acquisition of the fMR images. Functional imaging was performed on a 3 Tesla MRI system with a standard head coil using a T2*-weighted spiral-in/out sequence. The...

Comparisons of neural activity between humans and monkeys have usually relied on techniques using very different spatial and temporal scales. We report a method for scanning behaving macaques in a horizontal human 3 Tesla MR scanner to investigate neural processes involved in perception and to compare them to that of humans. Specifically, we have developed an apparatus for the animal to lie prone in the scanner bore, training procedures to minimize body movements while maintaining long periods of eye fixation (> 10 s), a mock training environment to acclimate the animal to the sights and sounds of the MRI, and surgical head-bolt implants for rigid head fixation that are MR-compatible. With the use of a 12 cm surface coil placed above the animal’s head, high-resolution functional (1.5 x 1.5 x 2.0 mm) and anatomical (0.5 mm3) scans are acquired in awake animals. Ongoing studies are exploring the organization of inferior temporal cortex with direct comparisons to human cortex. Other studies map retinotopicall...

In this study we investigated which brain structures are activated when the visual and vestibular systems receive contradictory head rotation information. Using a 1.5T scanner, we acquired T2* weighted single shot gradient echo EPI functional scans (TR/TE 3750/50ms, 124 volumes, matrix size 64x64, slice thickness 4mm) during a caloric stimulation paradigm (120 ml water of 20 degrees Celsius in 15 seconds). The image data was processed with SPM-99 on both single-subject and group analysis level. Each subject participated in two experiments, one with the eyes closed (vestibular input only) and one with the eyes open (vestibular and visual input). The caloric stimulation was quite effective and lead to a sense of rotation in all subjects, especially when the eyes were open. With the eyes closed, activation was seen in several cortical areas, corroborating previous reports in the literature, but not in the cerebellum. However, with the eyes open, activation was observed in several cortical areas, that partiall...

Functional MRI (fMRI) is increasingly used in neuroscience research and clinical investigations. However, current knowledge regarding reproducibility of fMRI data is poor. The few studies dealing with this issue were based on experiments that were not performed under strictly controlled conditions. The purpose of this project was to examine reproducibility of fMRI results of a motor function study with precisely measured mechanical and electrical outputs of the muscles. Subjects performed handgrip contractions using a custom-built handgrip device and matched pre-set target force levels with assistance of a visual feedback system (Liu et al., J. Neurosci. Methods 101: 49-57, 2000). Each subject repeated three trials of a force-matching task (50% maximal force) in one session and the same session was repeated three times on three different days. Force and EMG signals of finger flexor and extensor muscles were recorded online with the fMRI data. Reproducibility of fMRI, force, and EMG results was determined b...

Fueled by the recent and controversial brain-wide association studies in humans, the animal neuroimaging community has also begun questioning whether using larger sample sizes is necessary for ethical and effective scientific progress. In this opinion piece, we illustrate two opposing views on sample size extremes in MRI-based animal neuroimaging.