Correlation of Histomorphometric Changes with Diffusion Tensor Imaging for Evaluation of Blast-Induced Auditory Neurodegeneration in Chinchilla.

In the present study, we have evaluated the blast-induced auditory neurodegeneration in chinchilla by correlating the histomorphometric changes with diffusion tensor imaging. The chinchillas were exposed to single unilateral blast-overpressure (BOP) at ∼172dB peak sound pressure level (SPL) and the pathological changes were compared at 1 week and 1 month after BOP. The functional integrity of the auditory system was assessed by auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE). The axonal integrity was assessed using diffusion tensor imaging at regions of interests (ROIs) of the central auditory neuraxis (CAN) including the cochlear nucleus (CN), inferior colliculus (IC), and auditory cortex (AC). Post-BOP, cyto-architecture metrics such as viable cells, degenerating neurons, and apoptotic cells were quantified at the CAN ROIs using light microscopic studies using cresyl fast violet, hematoxylin and eosin, and modified Crossmon's trichrome stains. We observed mean ABR threshold shifts of 30- and 10-dB SPL at 1 week and 1 month after BOP, respectively. A similar pattern was observed in DPAOE amplitudes shift. In the CAN ROIs, diffusion tensor imaging studies showed a decreased axial diffusivity in CN 1 month after BOP and a decreased mean diffusivity and radial diffusivity at 1 week after BOP. However, morphometric measures such as decreased viable cells and increased degenerating neurons and apoptotic cells were observed at CN, IC, and AC. Specifically, increased degenerating neurons and reduced viable cells were high on the ipsilateral side when compared with the contralateral side. These results indicate that a single blast significantly damages structural and functional integrity at all levels of CAN ROIs.

Inferior Colliculus's Hypermetabolism: A New Finding on Brain FDG PET and Perfusion MRI in a Patient With COVID-19.

ABSTRACT: We present the case of a 64-year-old man presenting an episode of confusion during SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection with a positive oropharyngeal swab polymerase chain reaction test. He was hospitalized for dyspnea related to pneumonia demonstrated on chest CT. FDG PET performed after the confusion phase, but still in the COVID-19 (coronavirus disease 2019)-positive phase, showed high glucose metabolism of the inferior colliculi. Morphological MRI was normal. The first-pass perfusion MRI shows hyperperfusion of the inferior colliculi, corresponding to FDG PET hypermetabolism.

Brain mapping of auditory steady-state responses: A broad view of cortical and subcortical sources.

Auditory steady-state responses (ASSRs) are evoked brain responses to modulated or repetitive acoustic stimuli. Investigating the underlying neural generators of ASSRs is important to gain in-depth insight into the mechanisms of auditory temporal processing. The aim of this study is to reconstruct an extensive range of neural generators, that is, cortical and subcortical, as well as primary and non-primary ones. This extensive overview of neural generators provides an appropriate basis for studying functional connectivity. To this end, a minimum-norm imaging (MNI) technique is employed. We also present a novel extension to MNI which facilitates source analysis by quantifying the ASSR for each dipole. Results demonstrate that the proposed MNI approach is successful in reconstructing sources located both within (primary) and outside (non-primary) of the auditory cortex (AC). Primary sources are detected in different stimulation conditions (four modulation frequencies and two sides of stimulation), thereby demonstrating the robustness of the approach. This study is one of the first investigations to identify non-primary sources. Moreover, we show that the MNI approach is also capable of reconstructing the subcortical activities of ASSRs. Finally, the results obtained using the MNI approach outperform the group-independent component analysis method on the same data, in terms of detection of sources in the AC, reconstructing the subcortical activities and reducing computational load.

Depth relationships and measures of tissue thickness in dorsal midbrain.

Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distances from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for delineating depth for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.

The association between subcortical and cortical fMRI and lifetime noise exposure in listeners with normal hearing thresholds.

In animal models, exposure to high noise levels can cause permanent damage to hair-cell synapses (cochlear synaptopathy) for high-threshold auditory nerve fibers without affecting sensitivity to quiet sounds. This has been confirmed in several mammalian species, but the hypothesis that lifetime noise exposure affects auditory function in humans with normal audiometric thresholds remains unconfirmed and current evidence from human electrophysiology is contradictory. Here we report the auditory brainstem response (ABR), and both transient (stimulus onset and offset) and sustained functional magnetic resonance imaging (fMRI) responses throughout the human central auditory pathway across lifetime noise exposure. Healthy young individuals aged 25-40 years were recruited into high (n = 32) and low (n = 30) lifetime noise exposure groups, stratified for age, and balanced for audiometric threshold up to 16 kHz fMRI demonstrated robust broadband noise-related activity throughout the auditory pathway (cochlear nucleus, superior olivary complex, nucleus of the lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). fMRI responses in the auditory pathway to broadband noise onset were significantly enhanced in the high noise exposure group relative to the low exposure group, differences in sustained fMRI responses did not reach significance, and no significant group differences were found in the click-evoked ABR. Exploratory analyses found no significant relationships between the neural responses and self-reported tinnitus or reduced sound-level tolerance (symptoms associated with synaptopathy). In summary, although a small effect, these fMRI results suggest that lifetime noise exposure may be associated with central hyperactivity in young adults with normal hearing thresholds.

18F-FDG PET Imaging of the Inferior Colliculus in Asymmetric Hearing Loss.

Our purpose was to use PET to evaluate the glucose metabolism of the inferior colliculus (IC) and primary auditory cortex (PAC) in patients with asymmetric hearing loss (AHL). Methods: Normalized regional 18F-FDG uptake of the IC and PAC (reference: cerebellum) was assessed in 13 subjects with AHL using a fully digital clinical PET/CT system. Results: Regional metabolism of both the IC and the PAC was significantly reduced contralateral to the most hearing-impaired ear compared with the ipsilateral side. Duration of deafness correlated positively with metabolism of the contralateral PAC but not with metabolism of the ipsilateral PAC or either of the ICs. Conclusion: Fully digital, high-resolution clinical PET scanners allow for investigating small brain stem nuclei. AHL has a significant impact on the regional glucose metabolism of the auditory pathway. Mitigation of this effect by a longer duration of deafness might indicate reorganization at the cortical level.

Impaired Subcortical Detection of Auditory Changes in Schizophrenia but Not in Major Depression.

The mismatch negativity is a cortical response to auditory changes and its reduction is a consistent finding in schizophrenia. Recent evidence revealed that the human brain detects auditory changes already at subcortical stages of the auditory pathway. This finding, however, raises the question where in the auditory hierarchy the schizophrenic deficit first evolves and whether the well-known cortical deficit may be a consequence of dysfunction at lower hierarchical levels. Finally, it should be resolved whether mismatch profiles differ between schizophrenia and affective disorders which exhibit auditory processing deficits as well. We used functional magnetic resonance imaging to assess auditory mismatch processing in 29 patients with schizophrenia, 27 patients with major depression, and 31 healthy control subjects. Analysis included whole-brain activation, region of interest, path and connectivity analysis. In schizophrenia, mismatch deficits emerged at all stages of the auditory pathway including the inferior colliculus, thalamus, auditory, and prefrontal cortex. In depression, deficits were observed in the prefrontal cortex only. Path analysis revealed that activation deficits propagated from subcortical to cortical nodes in a feed-forward mechanism. Finally, both patient groups exhibited reduced connectivity along this processing stream. Auditory mismatch impairments in schizophrenia already manifest at the subcortical level. Moreover, subcortical deficits contribute to the well-known cortical deficits and show specificity for schizophrenia. In contrast, depression is associated with cortical dysfunction only. Hence, schizophrenia and major depression exhibit different neural profiles of sensory processing deficits. Our findings add to a converging body of evidence for brainstem and thalamic dysfunction as a hallmark of schizophrenia.

Waxholm Space atlas of the rat brain auditory system: Three-dimensional delineations based on structural and diffusion tensor magnetic resonance imaging.

The mammalian auditory system comprises a complex network of brain regions. Interpretations and comparisons of experimental results from this system depend on appropriate anatomical identification of auditory structures. The Waxholm Space (WHS) atlas of the Sprague Dawley rat brain (Papp et al., Neuroimage 97:374-86, 2014) is an open access, three-dimensional reference atlas defined in an ex-vivo magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) volume. Version 2.0 of the atlas (Kjonigsen et al., Neuroimage 108:441-9, 2015) includes detailed delineations of the hippocampus and several major subcortical regions, but only few auditory structures. To amend this, we have delineated the complete ascending auditory system from the cochlea to the cerebral cortex. 40 new brain structure delineations have been added, and the delineations of 10 regions have been revised based on the interpretation of image features in the WHS rat brain MRI/DTI volumes. We here describe and validate the new delineations in relation to corresponding cell- and myelin-stained histological sections and previous literature. We found it possible to delineate all main regions and the majority of subregions and fibre tracts of the ascending auditory pathway, apart from the auditory cortex, for which delineations were extrapolated from a conventional two-dimensional atlas. By contrast, only parts of the descending pathways were discernible in the template. Version 3.0 of the atlas, with altogether 118 anatomical delineations, is shared via the NeuroImaging Tools and Resources Collaboratory (www.nitrc.org).

Hemangioblastoma of Cerebral Aqueduct Removed via Sitting, Supracerebellar Intracollicular Approach.

BACKGROUND: Tumors protruding into the cerebral aqueduct are rare, and tumors arising from within the cerebral aqueduct are rarer still. CASE DESCRIPTION: In this report, we discuss the presentation and clinical outcome of a 65-year-old man who presented to us with symptoms of hydrocephalus. Prior imaging had revealed a small enhancing nodule within the cerebral aqueduct. In the 6 months between initial imaging and our seeing the patient, the tumor demonstrated substantial interval growth, so the patient was offered resection. The tumor was accessed using a sitting, supracerebellar, intracollicular approach, which allowed for gross total resection of the mass without complication. Histopathology later revealed the lesion to be a hemangioblastoma. Two years after surgery, the patient was doing well with no neurologic deficits. CONCLUSIONS: We report the first case of an aqueductal hemangioblastoma and describe our use of a sitting, supracerebellar, intracollicular approach to access tumors occupying this cerebrospinal fluid space.

Relationship between auditory pathway fractional anisotropy and audibility in patients with cerebellopontine angle tumors on diffusion tensor imaging.

OBJECTIVE: Recent reports demonstrated that acoustic nerve disorders affect the auditory pathway on diffusion tensor imaging (DTI). The aim was to investigate whether auditory pathway fractional anisotropy (FA) values are associated with audibility in patients with cerebellopontine angle tumors. PATIENTS AND METHODS: Patients with cerebellopontine angle tumors were included in this retrospective study. Preoperatively, all patients underwent magnetic resonance imaging (MRI) including DTI. Two regions of interest on the lateral lemniscus (LL) and inferior colliculus (IC) were set bilaterally on DTI. FA values were calculated using software. Correlations between FA values and audibility were evaluated using Spearman's rank correlation coefficient. Statistical significance was defined as p < 0.05. RESULTS: Seventeen patients with cerebellopontine angle tumors were included in this study. FA values in the bilateral LL showed a significant negative correlation with hearing impairment severity (r = -0.758, -0.600, p < 0.05). FA values on the ipsilateral side of the IC showed a significant negative correlation with hearing impairment severity (r = -0.477, p < 0.05). FA values on the contralateral side of the IC did not correlate with hearing impairment severity (r = -0.201, p > 0.05). One patient with a low FA value on the contralateral side of the IC had postoperative hearing impairment despite good preoperative hearing ability. CONCLUSIONS: FA values in the bilateral LL and on the ipsilateral side of the IC reflected hearing impairment severity. Decreased FA values on the contralateral side of the IC might predict hearing impairment postoperatively.

Optogenetic auditory fMRI reveals the effects of visual cortical inputs on auditory midbrain response.

Sensory cortices contain extensive descending (corticofugal) pathways, yet their impact on brainstem processing - particularly across sensory systems - remains poorly understood. In the auditory system, the inferior colliculus (IC) in the midbrain receives cross-modal inputs from the visual cortex (VC). However, the influences from VC on auditory midbrain processing are unclear. To investigate whether and how visual cortical inputs affect IC auditory responses, the present study combines auditory blood-oxygenation-level-dependent (BOLD) functional MRI (fMRI) with cell-type specific optogenetic manipulation of visual cortex. The results show that predominant optogenetic excitation of the excitatory pyramidal neurons in the infragranular layers of the primary VC enhances the noise-evoked BOLD fMRI responses within the IC. This finding reveals that inputs from VC influence and facilitate basic sound processing in the auditory midbrain. Such combined optogenetic and auditory fMRI approach can shed light on the large-scale modulatory effects of corticofugal pathways and guide detailed electrophysiological studies in the future.

Subcortical sources dominate the neuroelectric auditory frequency-following response to speech.

Frequency-following responses (FFRs) are neurophonic potentials that provide a window into the encoding of complex sounds (e.g., speech/music), auditory disorders, and neuroplasticity. While the neural origins of the FFR remain debated, renewed controversy has reemerged after demonstration that FFRs recorded via magnetoencephalography (MEG) are dominated by cortical rather than brainstem structures as previously assumed. Here, we recorded high-density (64 ch) FFRs via EEG and applied state-of-the art source imaging techniques to multichannel data (discrete dipole modeling, distributed imaging, independent component analysis, computational simulations). Our data confirm a mixture of generators localized to bilateral auditory nerve (AN), brainstem inferior colliculus (BS), and bilateral primary auditory cortex (PAC). However, frequency-specific scrutiny of source waveforms showed the relative contribution of these nuclei to the aggregate FFR varied across stimulus frequencies. Whereas AN and BS sources produced robust FFRs up to ∼700 Hz, PAC showed weak phase-locking with little FFR energy above the speech fundamental (100 Hz). Notably, CLARA imaging further showed PAC activation was eradicated for FFRs >150 Hz, above which only subcortical sources remained active. Our results show (i) the site of FFR generation varies critically with stimulus frequency; and (ii) opposite the pattern observed in MEG, subcortical structures make the largest contribution to electrically recorded FFRs (AN ≥ BS > PAC). We infer that cortical dominance observed in previous neuromagnetic data is likely due to the bias of MEG to superficial brain tissue, underestimating subcortical structures that drive most of the speech-FFR. Cleanly separating subcortical from cortical FFRs can be achieved by ensuring stimulus frequencies are >150-200 Hz, above the phase-locking limit of cortical neurons.

[A case of Wernicke encephalopathy with hypoacusia and MR high intensity of the inferior colliculi that normalized after thiamine administration].

A 61-year-old man was admitted to our institution with progressive hypoacusia, double vision, and lightheadedness. Neurological examination on day 6 of his illness showed severe hypoacusia, mild confusion, ocular motility disorder, truncal ataxia and absence of a deep tendon reflex. MRI fluid-attenuated inversion recovery imaging revealed symmetrical high intensities in the tectum of the midbrain, involving the bilateral inferior colliculi and the bilateral medial thalami, which suggested Wernicke encephalopathy (WE). Thiamine was administered immediately after completion of the MRI, and the patients' hearing and other abnormal neurologic signs improved rapidly within a few days, except for the absence of the deep tendon reflex. Whole blood examination at admission revealed very low levels of vitamin B1. The patient was discharged on day 19, and MRI on day 39 showed the disappearance of the abnormal high intensities involving the bilateral inferior colliculi. The present case indicates that hypoacusia and abnormal MRI signal due to WE might be normalized by administration of thiamine a few days after the onset of symptoms.

Dissonance encoding in human inferior colliculus covaries with individual differences in dislike of dissonant music.

Harmony is one of the most fundamental elements of music that evokes emotional response. The inferior colliculus (IC) has been known to detect poor agreement of harmonics of sound, that is, dissonance. Electrophysiological evidence has implicated a relationship between a sustained auditory response mainly from the brainstem and unpleasant emotion induced by dissonant harmony. Interestingly, an individual's dislike of dissonant harmony of an individual correlated with a reduced sustained auditory response. In the current paper, we report novel evidence based on functional magnetic resonance imaging (fMRI) for such a relationship between individual variability in dislike of dissonance and the IC activation. Furthermore, for the first time, we show how dissonant harmony modulates functional connectivity of the IC and its association with behaviourally reported unpleasantness. The current findings support important contributions of low level auditory processing and corticofugal interaction in musical harmony preference.

The organization of frequency and binaural cues in the gerbil inferior colliculus.

The inferior colliculus (IC) is the common target of separate pathways that transmit different types of auditory information. Beyond tonotopy, little is known about the organization of response properties within the 3-dimensional layout of the auditory midbrain in most species. Through study of interaural time difference (ITD) processing, the functional properties of neurons can be readily characterized and related to specific pathways. To characterize the representation of ITDs relative to the frequency and hodological organization of the IC, the properties of neurons were recorded and the sites recovered histologically. Subdivisions of the IC were identified based on cytochrome oxidase (CO) histochemistry. The results were plotted within a framework formed by an MRI atlas of the gerbil brain. The central nucleus was composed of two parts, and lateral and dorsal cortical areas were identified. The lateral part of the central nucleus had the highest CO activity in the IC and a high proportion of neurons sensitive to ITDs. The medial portion had lower CO activity and fewer ITD-sensitive neurons. A common tonotopy with a dorsolateral to ventromedial gradient of low to high frequencies spanned the two regions. The distribution of physiological responses was in close agreement with known patterns of ascending inputs. An understanding of the 3-dimensional organization of the IC is needed to specify how the single tonotopic representation in the IC central nucleus leads to the multiple tonotopic representations in core areas of the auditory cortex.

Effects of long-term salicylate administration on synaptic ultrastructure and metabolic activity in the rat CNS.

Tinnitus is associated with neural hyperactivity in the central nervous system (CNS). Salicylate is a well-known ototoxic drug, and we induced tinnitus in rats using a model of long-term salicylate administration. The gap pre-pulse inhibition of acoustic startle test was used to infer tinnitus perception, and only rats in the chronic salicylate-treatment (14 days) group showed evidence of experiencing tinnitus. After small animal positron emission tomography scans were performed, we found that the metabolic activity of the inferior colliculus (IC), the auditory cortex (AC), and the hippocampus (HP) were significantly higher in the chronic treatment group compared with saline group (treated for 14 days), which was further supported by ultrastructural changes at the synapses. The alterations all returned to baseline 14 days after the cessation of salicylate-treatment (wash-out group), indicating that these changes were reversible. These findings indicate that long-term salicylate administration induces tinnitus, enhanced neural activity and synaptic ultrastructural changes in the IC, AC, and HP of rats due to neuroplasticity. Thus, an increased metabolic rate and synaptic transmission in specific areas of the CNS may contribute to the development of tinnitus.

[Manganese enhanced magnetic resonance imaging investigation in the central auditory pathway of the cat].

OBJECTIVE: To compare enhancement of the central auditory pathway in cats receiving auditory stimulation between manganese enhanced magnetic resonance imaging (MEMRI) with intraperitoneal manganese injection route and MEMRI with intratympanic manganese injection route, and investigate the optimal method for displaying enhancement of the central auditory pathway. METHODS: Twenty-seven normal hearing adult cats were randomly divided into three groups, receiving intraperitoneal manganese injection, left intratympanic manganese injection or left intratympanic gadolinium injection respectively.All cats received white noise stimulation of 80 dB in twenty-four hours after injection.Three dimensionally coronal T1-weighted imaging of the cat brain was obtained with an animal dedicated MRI scanner.The signal noise ratios (SNRs) of bilateral cochlear nuclei (CN), dorsal nuclei of the trapezoid bodies (DNTB), caudal colliculi (CC) and auditory cortices (AC) were measured on reconstructed images and compared. RESULTS: Obvious increased SNRs on both sides were shown in intraperitoneal mangasese injection group while left predilection was shown in intratympanic manganese injection group: left CN 45.7±6.0, 37.4±11.9, 23.9±2.7, F=17.694, P=0.000; left DNTB 50.5±11.2, 37.1±11.2, 27.6±7.3, F=11.781, P=0.000; left CC 37.6±3.9, 22.6±3.1, 17.9±0.7, F=111.898, P=0.000; left AC 27.7±2.5, 17.3±2.3, 14.5±1.0, F=105.132, P=0.000; right CN 42.7±8.3, 23.9±3.0, 22.7±2.1, F=41.492, P=0.000; right DNTB 44.1±8.3, 21.9±3.0, 23.9±4.0, F=27.862, P=0.000; right CC 38.0±4.0, 21.9±3.0, 17.6±0.9, F=120.032, P=0.000; right AC 26.7±3.4, 17.1±2.9, 14.9±1.3, F=64.587, P=0.000.Compared with the left intratympanic gadolinium injection group, the intraperitoneal manganese injection group showed higher SNRs in bilateral CN and CC (P<0.05), and the left intratympanic manganese injection group showed higher SNRs in left CN, AC and bilateral CC.The SNRs of right CN, bilateral DNTB, CC and AC were significantly higher in the intraperitoneal manganese injection group than those in the left intratympanic manganese injection group (P<0.05). CONCLUSION: MEMRI with intraperitoneal manganese injection might be the optimal method for displaying enhancement of the central auditory pathway in cats receiving auditory stimulation.

An animal model of central auditory pathway imaging in the rat brain by high resolution small animal positron emission tomography.

CONCLUSIONS: Our study demonstrated that high resolution animal positron emission tomography (PET) can non-invasively assess the change in glucose metabolism of the central auditory pathway including the inferior colliculus and auditory cortex in the rat. OBJECTIVES: The traditional in vitro approach with immunohistochemical staining or autoradiography to assess chronological changes or topographic arrangement of central auditory pathway required sacrificing a large number of animals. Inter-individual difference is also a major concern. Therefore, development of an in vivo animal model using PET imaging would be a rational method to overcome these shortcomings. MATERIALS AND METHODS: Small animal PET scan using (18)F-fluorodeoxyglucose (FDG) as a functional marker was performed in rats. Each animal was serially scanned before and after unilateral cochlear ablation, with and without acoustic stimulation. The images were analyzed by the region of interest (ROI) method. Ratios of radioactivity at the inferior colliculus and auditory cortex and a referenced cerebral cortex between bilateral hemispheres were measured. RESULTS: These scans demonstrated several brain structures including the inferior colliculus (IC) and cortex (B). Moreover, unilateral cochlear ablation decreased the radioactivity at contralateral IC and auditory cortex (C) areas. Differences may reach 33% in IC and 27% in C, and average radioactivity ratios were 1.24+/-0.08 and 1.18+/-0.07 in selected adjacent sections, respectively.

Bionic ear imaging.

PURPOSE: The aim of this study was to illustrate the different imaging features of middle and inner ear implants, brainstem implants and inferior colliculus implants. MATERIALS AND METHODS: We retrospectively reviewed the computed tomography (CT) images of 468 patients with congenital or acquired transmissive or neurosensory hearing loss who underwent surgery. The implants examined were: 22 Vibrant Soundbridge implants, 5 at the long limb of the incus and 17 at the round window, 350 cochlear implants, 95 brainstem implants and 1 implant at the inferior colliculus. All patients underwent a postoperative CT scan (single or multislice scanner) and/or a Dentomaxillofacial cone-beam CT scan (CBCT) (axial and multiplanar reconstruction), and/or a plain-film radiography to visualise the correct position of the implant. RESULTS: The CBCT scan depicts Vibrant site of implant better than plain-film radiography, with a lower radiation dose compared to CT. For cochlear implants, a single plain radiograph in the Stenvers projection can directly visualise the electrodes in the cochlea. All patients with brainstem or inferior colliculus implants underwent postoperative CT to exclude complications and the assess correct implantation, but the follow-up of these implants can be performed by plain radiography alone. CONCLUSIONS: CT and CBCT scans are reliable and relatively fast methods for precisely determining the location of middle ear implants. CBCT is preferable to CT because of the lower radiation dose administered; a single plain-film radiograph is enough to visualise and follow-up cochlear, brainstem and inferior colliculus implants.

Using a white matter reference to remove the dependency of global signal on experimental conditions in SPECT analyses.

Proportional scaling models are often used in functional imaging studies to remove confounding of local signals by global effects. It is generally assumed that global effects are uncorrelated with experimental conditions. However, when the global effect is estimated by the global signal, defined as the intracerebral average, incorrect inference may result from the dependency of the global signal on preexisting conditions or experimental manipulations. In this paper, we propose a simple alternative method of estimating the global effect to be used in a proportional scaling model. Specifically, by defining the global signal with reference strictly to a white matter region within the centrum semiovale, the dependency is removed in experiments where white matter is unaffected by the disease effect or experimental treatments. The increase in the ability to detect changes in regional blood flow is demonstrated in a SPECT study of healthy and ill Gulf War veterans in whom it is suspected that brain abnormalities influence the traditional calculation of the global signal. Controlling for the global effect, ill veterans have significantly lower intracerebral averages than healthy controls (P = 0.0038), evidence that choice of global signal has an impact on inference. Scaling by the modified global signal proposed here results in an increase in sensitivity leading to the identification of several regions in the insula and frontal cortex where ill veterans have significantly lower SPECT emissions. Scaling by the traditional global signal results in the loss of sensitivity to detect these regional differences. Advantages of this alternative method are its computational simplicity and its ability to be easily integrated into existing analysis frameworks such as SPM.