Lithium from breast-milk inhibits thyroid iodine uptake and hormone production, which are remedied by maternal iodine supplementation.

BACKGROUND: Lithium is especially taken as a maintenance medication for Bipolar Disorder. In women with bipolar disorder, lithium is often effective during postpartum period, but breast-feeding for medicated mothers is controversial because of harmful effects for her child. At present, the biological mechanisms of lithium are not well-understood, affecting its usage and overall health implications. PROCEDURE: We developed a rat lithium and breast-feeding model at human therapeutic levels to study the effects of lithium exposure through breast-milk on pups' thyroid function. Novel laser analytical spectroscopy, along with traditional blood and immunohistochemical tests, were applied to further investigate the mechanisms behind the thyroid dysfunction. Maternal iodine supplementation was evaluated as a therapeutic method to address the pups' thyroid dysfunction. RESULTS: Pups exposed to lithium via breastmilk, even with the dam on a sub-therapeutic level, experienced weight gain, reduced blood thyroxine (T4 ), and elevated blood urea nitrogen, indicating effects on thyroid and kidney function. We show that lithium inhibited iodine uptake by thyroid follicles, initiating a mechanism that reduced iodination of tyrosine, thyroglobulin cleavage, and thyroid hormone production. Importantly, infant thyroid function can be significantly improved by administering supplementary iodine to the medicated dam's diet during breast-feeding. CONCLUSION: These results elucidate the mechanisms of lithium in thyroid function, provide valuable information on use postpartum, and suggest a clinically applicable remedy to side-effects. The results are particularly important for patients (and their infants) who respond well to lithium and need, or choose, to breast-feed.

Spectroscopic and microscopic examination of teeth exposed to green tea at different temperatures.

Tea is a popular beverage consumed at different temperatures. The effect of tea on teeth at different temperatures has not been studied previously. The present study used an in vitro green tea immersed tooth model at different tea temperatures (hot and cold) compared to an in vivo tea administration model allowing rats to drink tea over the course of a week. The elements present in tea leaves were identified by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and compared to the elements in teeth (enamel surface) using Laser-Induced Breakdown Spectroscopy (LIBS). Here, LIBS demonstrated in vivo and in vitro green tea treatments resulted in a significant increase in the mineral elements found in enamel. For the in vitro assessment, elements in enamel varied based on cold-tea and hot-tea treatment; however, hot water reduced the elements in enamel. Atomic force microscopy found the in vivo tea group had a higher roughness average (RA) compared with the in vivo water group. Cold tea and hot tea in vitro groups demonstrated lower RA than in vitro water controls. Scanning electron microscopy found hot water induced cracks more than 1.3µm in enamel while cold tea and hot tea promoted the adhering of extrinsic matter to teeth. Overall, teeth treated to high temperature lost the mineral phase leading to demineralization. Our results indicate that green tea protects enamel, but its protective action in dental structures is enhanced at cold temperature.

Functional magnetic resonance imaging of enhanced central auditory gain and electrophysiological correlates in a behavioral model of hyperacusis.

Hyperacusis is a debilitating hearing condition in which normal everyday sounds are perceived as exceedingly loud, annoying, aversive or even painful. The prevalence of hyperacusis approaches 10%, making it an important, but understudied medical condition. To noninvasively identify the neural correlates of hyperacusis in an animal model, we used sound-evoked functional magnetic resonance imaging (fMRI) to locate regions of abnormal activity in the central nervous system of rats with behavioral evidence of hyperacusis induced with an ototoxic drug (sodium salicylate, 250 mg/kg, i.p.). Reaction time-intensity measures of loudness-growth revealed behavioral evidence of salicylate-induced hyperacusis at high intensities. fMRI revealed significantly enhanced sound-evoked responses in the auditory cortex (AC) to 80 dB SPL tone bursts presented at 8 and 16 kHz. Sound-evoked responses in the inferior colliculus (IC) were also enhanced, but to a lesser extent. To confirm the main results, electrophysiological recordings of spike discharges from multi-unit clusters were obtained from the central auditory pathway. Salicylate significantly enhanced tone-evoked spike-discharges from multi-unit clusters in the AC from 4 to 30 kHz at intensities ≥60 dB SPL; less enhancement occurred in the medial geniculate body (MGB), and even less in the IC. Our results demonstrate for the first time that non-invasive sound-evoked fMRI can be used to identify regions of neural hyperactivity throughout the brain in an animal model of hyperacusis.

The human amygdala disconnecting from auditory cortex preferentially discriminates musical sound of uncertain emotion by altering hemispheric weighting.

How do humans discriminate emotion from non-emotion? The specific psychophysical cues and neural responses involved with resolving emotional information in sound are unknown. In this study we used a discrimination psychophysical-fMRI sparse sampling paradigm to locate threshold responses to happy and sad acoustic stimuli. The fine structure and envelope of auditory signals were covaried to vary emotional certainty. We report that emotion identification at threshold in music utilizes fine structure cues. The auditory cortex was activated but did not vary with emotional uncertainty. Amygdala activation was modulated by emotion identification and was absent when emotional stimuli were chance identifiable, especially in the left hemisphere. The right hemisphere amygdala was considerably more deactivated in response to uncertain emotion. The threshold of emotion was signified by a right amygdala deactivation and change of left amygdala greater than right amygdala activation. Functional sex differences were noted during binaural uncertain emotional stimuli presentations, where the right amygdala showed larger activation in females. Negative control (silent stimuli) experiments investigated sparse sampling of silence to ensure modulation effects were inherent to emotional resolvability. No functional modulation of Heschl's gyrus occurred during silence; however, during rest the amygdala baseline state was asymmetrically lateralized. The evidence indicates changing hemispheric activation and deactivation patterns between the left and right amygdala is a hallmark feature of discriminating emotion from non-emotion in music.

Functional MRI Investigation of Audiovisual Interactions in Auditory Midbrain.

The brain integrates information from different sensory modalities to form a representation of the environment and facilitate behavioral responses. The auditory midbrain or inferior colliculus (IC) is a pivotal station in the auditory system, integrating ascending and descending information from various auditory sources and cortical systems. The present study investigated the modulation of auditory responses in the IC by visual stimuli of different frequencies and intensities in rats using functional MRI (fMRI). Low-frequency (1 Hz) high-intensity visual stimulus suppressed IC auditory responses. However, high-frequency (10 Hz) or low-intensity visual stimuli did not alter the IC auditory responses. This finding demonstrates that cross-modal processing occurs in the IC in a manner that depends on the stimulus. Furthermore, only low-frequency high-intensity visual stimulus elicited responses in non-visual cortical regions, suggesting that the above cross-modal modulation effect may arise from top-down cortical feedback. These fMRI results provide insight to guide future studies of cross-modal processing in sensory pathways.

Auditory-visual convergence at the superior colliculus in rat using functional MRI.

The superior colliculus (SC) of the midbrain has been a model structure for multisensory processing. Many neurons in the intermediate and deep SC layers respond to two or more of auditory, visual, and somatosensory stimuli as assessed by electrophysiology. In contrast, noninvasive and large field of view functional magnetic resonance imaging (fMRI) studies have focused on multisensory processing in the cortex. In this study, we applied blood oxygenation leveldependent (BOLD) fMRI on Sprague-Dawley rats receiving monaural (auditory) and binocular (visual) stimuli to study subcortical multisensory processing. Activation was observed in the left superior olivary complex, lateral lemniscus, and inferior colliculus and both hemispheres of the superior colliculus during auditory stimulation. The SC response was bilateral even though the stimulus was monaural. During visual stimulation, activation was observed in both hemispheres of the SC and lateral geniculate nucleus. In both hemispheres of the SC, the number of voxels in the activation area $( \mathrm {p}<10 -8$) and BOLD signal changes $( \mathrm {p}<0.01)$ were significantly greater during visual than auditory stimulation. These results provide functional imaging evidence that the SC is a site of auditoryvisual convergence due to its involvement in both auditory and visual processing. The auditory and visual fMRI activations likely reflect the firing of unisensory and multisensory neurons in the SC. The present study lays the groundwork for noninvasive functional imaging studies of multisensory convergence and integration in the SC.

Spectroscopic examination of enamel staining by coffee indicates dentin erosion by sequestration of elements.

The mechanism of coffee eliciting erosion on teeth is unclear as few studies have investigated the direct effect of coffee on enamel and dentin structures. The present study identified how coffee, the most popular beverage worldwide, induces staining and erosion on teeth. We show the grade of erosion of molars and incisors in Sprague Dawley rats from two different age groups, young (four weeks) and old (six months). We quantified the concentration of metals contained in coffee by mass spectrometry (ICP-MS). To determine elemental content in enamel (i.e. superficial) and dentin (i.e. substructure), we used Laser-induced Breakdown Spectroscopy (LIBS) and X-ray fluorescence (XRF) spectroscopy, respectively. For LIBS, a significant decrease of Ca, P, and Na was observed in the young coffee group relative to age-matched controls, whereas a significant increase in Mn, Fe, and K was observed. In the old coffee group, a significant increase of Mg, Fe, and K was observed along with a decrease of Mg, Ca, P, Na, Sr and Zn. For XRF, a significant decrease of the Ca/P ratio in the coffee group was observed. Spectroscopy results were correlated with scanning electron microscopy (SEM) and histological analysis. The SEM analysis showed pores and open spaces between young and old coffee groups, respectively. Thinning of enamel layers, loss of continuity in the enamel-dentin-junction, and wide spaces in dentin tubules with coffee use was found histologically. Coffee induces decalcification of teeth that corresponds to erosion, exposing the dentin structure by reducing enamel. Coffee immersion demonstrated an intrinsic staining in dentin by metal deposition.

Chronic exposure to broadband noise at moderate sound pressure levels spatially shifts tone-evoked responses in the rat auditory midbrain.

Noise-induced hearing disorders are a significant public health concern. One cause of such disorders is exposure to high sound pressure levels (SPLs) above 85 dBA for eight hours/day. High SPL exposures occur in occupational and recreational settings and affect a substantial proportion of the population. However, an even larger proportion is exposed to more moderate SPLs for longer durations. Therefore, there is significant need to better understand the impact of chronic, moderate SPL exposures on auditory processing, especially in the absence of hearing loss. In this study, we applied functional magnetic resonance imaging (fMRI) with tonal acoustic stimulation on an established broadband rat exposure model (65 dB SPL, 30 kHz low-pass, 60 days). The auditory midbrain response of exposed subjects to 7 kHz stimulation (within exposure bandwidth) shifts dorsolaterally to regions that typically respond to lower stimulation frequencies. This shift is quantified by a region of interest analysis that shows that fMRI signals are higher in the dorsolateral midbrain of exposed subjects and in the ventromedial midbrain of control subjects (p<0.05). Also, the center of the responsive region in exposed subjects shifts dorsally relative to that of controls (p<0.05). A similar statistically significant shift (p<0.01) is observed using 40 kHz stimulation (above exposure bandwidth). The results suggest that high frequency midbrain regions above the exposure bandwidth spatially expand due to exposure. This expansion shifts lower frequency regions dorsolaterally. Similar observations have previously been made in the rat auditory cortex. Therefore, moderate SPL exposures affect auditory processing at multiple levels, from the auditory cortex to the midbrain.

Long-term, passive exposure to non-traumatic acoustic noise induces neural adaptation in the adult rat medial geniculate body and auditory cortex.

Exposure to loud sounds can lead to permanent hearing loss, i.e., the elevation of hearing thresholds. Exposure at more moderate sound pressure levels (SPLs) (non-traumatic and within occupational limits) may not elevate thresholds, but could in the long-term be detrimental to speech intelligibility by altering its spectrotemporal representation in the central auditory system. In support of this, electrophysiological and behavioral changes following long-term, passive (no conditioned learning) exposure at moderate SPLs have recently been observed in adult animals. To assess the potential effects of moderately loud noise on the entire auditory brain, we employed functional magnetic resonance imaging (fMRI) to study noise-exposed adult rats. We find that passive, pulsed broadband noise exposure for two months at 65 dB SPL leads to a decrease of the sound-evoked blood oxygenation level-dependent fMRI signal in the thalamic medial geniculate body (MGB) and in the auditory cortex (AC). This points to the thalamo-cortex as the site of the neural adaptation to the moderately noisy environment. The signal reduction is statistically significant during 10 Hz pulsed acoustic stimulation (MGB: p<0.05, AC: p<10(-4)), but not during 5 Hz stimulation. This indicates that noise exposure has a greater effect on the processing of higher pulse rate sounds. This study has enhanced our understanding of functional changes following exposure by mapping changes across the entire auditory brain. These findings have important implications for speech processing, which depends on accurate processing of sounds with a wide spectrum of pulse rates.

Noninvasive fMRI investigation of interaural level difference processing in the rat auditory subcortex.

OBJECTIVE: Interaural level difference (ILD) is the difference in sound pressure level (SPL) between the two ears and is one of the key physical cues used by the auditory system in sound localization. Our current understanding of ILD encoding has come primarily from invasive studies of individual structures, which have implicated subcortical structures such as the cochlear nucleus (CN), superior olivary complex (SOC), lateral lemniscus (LL), and inferior colliculus (IC). Noninvasive brain imaging enables studying ILD processing in multiple structures simultaneously. METHODS: In this study, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is used for the first time to measure changes in the hemodynamic responses in the adult Sprague-Dawley rat subcortex during binaural stimulation with different ILDs. RESULTS AND SIGNIFICANCE: Consistent responses are observed in the CN, SOC, LL, and IC in both hemispheres. Voxel-by-voxel analysis of the change of the response amplitude with ILD indicates statistically significant ILD dependence in dorsal LL, IC, and a region containing parts of the SOC and LL. For all three regions, the larger amplitude response is located in the hemisphere contralateral from the higher SPL stimulus. These findings are supported by region of interest analysis. fMRI shows that ILD dependence occurs in both hemispheres and multiple subcortical levels of the auditory system. This study is the first step towards future studies examining subcortical binaural processing and sound localization in animal models of hearing.

High fidelity tonotopic mapping using swept source functional magnetic resonance imaging.

Tonotopy, the topographic encoding of sound frequency, is the fundamental property of the auditory system. Invasive techniques lack the spatial coverage or frequency resolution to rigorously investigate tonotopy. Conventional auditory fMRI is corrupted by significant image distortion, sporadic acoustic noise and inadequate frequency resolution. We developed an efficient and high fidelity auditory fMRI method that integrates continuous frequency sweeping stimulus, distortion free MRI sequence with stable scanner noise and Fourier analysis. We demonstrated this swept source imaging (SSI) in the rat inferior colliculus and obtained tonotopic maps with ~2 kHz resolution and 40 kHz bandwidth. The results were vastly superior to those obtained by conventional fMRI mapping approach and in excellent agreement with invasive findings. We applied SSI to examine tonotopic injury following developmental noise exposure and observed that the tonotopic organization was significantly disrupted. With SSI, we also observed the subtle effects of sound pressure level on tonotopic maps, reflecting the complex neuronal responses associated with asymmetric tuning curves. This in vivo and noninvasive technique will greatly facilitate future investigation of tonotopic plasticity and disorders and auditory information processing. SSI can also be adapted to study topographic organization in other sensory systems such as retinotopy and somatotopy.

BOLD temporal dynamics of rat superior colliculus and lateral geniculate nucleus following short duration visual stimulation.

BACKGROUND: The superior colliculus (SC) and lateral geniculate nucleus (LGN) are important subcortical structures for vision. Much of our understanding of vision was obtained using invasive and small field of view (FOV) techniques. In this study, we use non-invasive, large FOV blood oxygenation level-dependent (BOLD) fMRI to measure the SC and LGN's response temporal dynamics following short duration (1 s) visual stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Experiments are performed at 7 tesla on Sprague Dawley rats stimulated in one eye with flashing light. Gradient-echo and spin-echo sequences are used to provide complementary information. An anatomical image is acquired from one rat after injection of monocrystalline iron oxide nanoparticles (MION), a blood vessel contrast agent. BOLD responses are concentrated in the contralateral SC and LGN. The SC BOLD signal measured with gradient-echo rises to 50% of maximum amplitude (PEAK) 0.2±0.2 s before the LGN signal (p<0.05). The LGN signal returns to 50% of PEAK 1.4±1.2 s before the SC signal (p<0.05). These results indicate the SC signal rises faster than the LGN signal but settles slower. Spin-echo results support these findings. The post-MION image shows the SC and LGN lie beneath large blood vessels. This subcortical vasculature is similar to that in the cortex, which also lies beneath large vessels. The LGN lies closer to the large vessels than much of the SC. CONCLUSIONS/SIGNIFICANCE: The differences in response timing between SC and LGN are very similar to those between deep and shallow cortical layers following electrical stimulation, which are related to depth-dependent blood vessel dilation rates. This combined with the similarities in vasculature between subcortex and cortex suggest the SC and LGN timing differences are also related to depth-dependent dilation rates. This study shows for the first time that BOLD responses in the rat SC and LGN following short duration visual stimulation are temporally different.