High-resolution reduced field of view diffusion tensor imaging using spatially selective RF pulses.

PURPOSE: Diffusion tensor imaging (DTI) plays a vital role in identifying white matter fiber bundles. Achievable imaging resolution and imaging time demands remain the major challenges in detecting small fiber bundles with current clinical DTI sequences. METHODS: A novel reduced field of view ultra-high-resolution DTI technique named eZOOM (elliptically refocused zonally oblique multislice) was developed. A small circular disk was imaged using spatially selective radiofrequency (RF) pulses, reducing the imaging matrix size. The frequency profile of the spectral-spatial refocusing RF pulse provided intrinsic fat suppression, eliminating the need for fat saturation pulses. RESULTS: Multislice DTI at a resolution of 0.35 × 0.35 mm in a celery fiber phantom was successfully performed by scanning an 8-cm field of view at 3T. An adequate diffusion-to-noise ratio (DNR >20) was achieved for a 25-min acquisition using a direct-sampling RF receiver. Human subjects (n = 7) were scanned at resolutions of 0.47 × 0.47 mm having a DNR <20 within a 75-min scanning time, requiring further enhancements to increase the signal-to-noise ratio. CONCLUSIONS: The new eZOOM-DTI method offers multislice DTI at ultra-high imaging resolutions substantially exceeding those available with current echo-planar DTI techniques. Parallel and fast spin echo methods can be combined with eZOOM to improve SNR and DNR in humans.

Motor homunculus: passive mapping in healthy volunteers by using functional MR imaging--initial results.

PURPOSE: To determine the concurrence of activation in the primary motor cortex, induced by paradigms of active and passive movement of extremities, by using blood oxygen level-dependent functional magnetic resonance (MR) imaging. MATERIALS AND METHODS: The HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained from the participating volunteers. Functional MR imaging data were collected from 11 healthy volunteers (four women, seven men; age range, 24-42 years) during active and passive movements of hand, elbow, shoulder, ankle, knee, and hip. These data were then mapped onto three-dimensional anatomic images. Volumes of activation were determined by using cross-correlation analysis at a coefficient threshold of 0.4 (P < .01). Regions of interest were drawn in pre- and postcentral gyri based on anatomic criteria. The mean number of activated voxels in the pre- and postcentral gyri induced by active and passive movements was compared by using Wilcoxon analysis. Concurrence ratios and proportional ratios of activation between active and passive movements were calculated for each somatotopic location. RESULTS: Primary motor cortex activation tended to increase with active compared with passive movements, although in the precentral gyrus, hand, elbow, and shoulder movements showed no statistically significant difference in mean number of activated voxels. In the postcentral gyrus, only the shoulder revealed a significant difference (P < .05). Concurrence ratios (activation volume overlap of two tasks/combined activation area of both tasks) ranged from 0.44 to 0.57. Proportional ratios (activation volume overlap of passive task with active task/total activation volume of passive task) ranged from 0.64 to 0.82. CONCLUSION: Passive movement paradigms may be an alternative to or complement to active movement tasks in patient populations.

Feasibility of auditory cortical stimulation for the treatment of tinnitus.

OBJECTIVES: To investigate the feasibility and safety of an implantable epidural cortical stimulator for the treatment of severe tinnitus. STUDY DESIGN: Prospective, controlled, single-blinded study of cortical stimulation for 4 weeks, and then an open-label stimulation period. SETTING: Tertiary care referral center. PATIENTS: Adults (n = 8) with constant tinnitus of at least 1 year with a tinnitus reaction questionnaire score greater than 33. Tinnitus was predominantly unilateral with a frequency less than 8,000 Hz. INTERVENTIONS: Surgical implantation of an investigational epidural electrode over the posterior superior temporal gyrus using functional magnetic resonance imaging targeting. A 2-week stimulation period alternated with a 2-week sham period in random order to which subjects were blinded. This was followed by continuous stimulation with parameter adjustments to maximize tinnitus suppression. MAIN OUTCOME MEASURE: Subjective rating of tinnitus severity, loudness, and device efficacy. Objective measures of hearing thresholds, tinnitus frequency, loudness, and minimum masking levels. Outcome measures using the Tinnitus Handicap Questionnaire, Tinnitus Reaction Questionnaire, and Beck Depression Inventory. RESULTS: There were no effects of stimulation during the 4-week blinded period. With continuous chronic stimulation, 2 patients had persistent reduction of pure-tone tinnitus, and 6 patients had short periods of total tinnitus suppression. Significant improvements in the Beck Depression Inventory and tinnitus questionnaires were found, although objective measures of tinnitus loudness remained fairly stable. No surgical or stimulation-related complications were noted. CONCLUSION: Chronic electrical stimulation of the secondary auditory cortex seems safe and warrants further investigation as a potential therapeutic intervention for the suppression of tinnitus.

The Impact of Intracranial Tumor Proximity to White Matter Tracts on Morbidity and Mortality: A Retrospective Diffusion Tensor Imaging Study.

Background: Using diffusion tensor imaging (DTI) in neurosurgical planning allows identification of white matter tracts and has been associated with a reduction in postoperative functional deficits. Objective: This study explores the relationship between the lesion-to-tract distance (LTD) and postoperative morbidity and mortality in patients with brain tumors in order to evaluate the role of DTI in predicting postoperative outcomes. Methods: Adult patients with brain tumors (n = 60) underwent preoperative DTI. Three major white matter pathways (superior longitudinal fasciculi [SLF], cingulum, and corticospinal tract) were identified using DTI images, and the shortest LTD was measured for each tract. Postoperative morbidity and mortality information was collected from electronic medical records. Results: The ipsilesional corticospinal tract LTD and left SLF LTD were significantly associated with the occurrence rate of total postoperative motor (P = .018) and language (P < .001) deficits, respectively. The left SLF LTD was also significantly associated with the occurrence rate of new postoperative language deficits (P = .003), and the LTD threshold that best predicted this occurrence was 1 cm (P < .001). Kaplan­Meier log-rank survival analyses in patients having high-grade tumors demonstrated a significantly higher mortality for patients with a left SLF LTD <1 cm (P = .01). Conclusion: Measuring tumor proximity to major white matter tracts using DTI can inform clinicians of the likelihood of postoperative functional deficits. A distance of 1 cm or less from eloquent white matter structures most significantly predicts the occurrence of new deficits with current surgical and imaging techniques.

Differential representation of speech sounds in the human cerebral hemispheres.

Various methods in auditory neuroscience have been used to gain knowledge about the structure and function of the human auditory cortical system. Regardless of method, hemispheric differences are evident in the normal processing of speech sounds. This review article, augmented by the authors' own work, provides evidence that asymmetries exist in both cortical and subcortical structures of the human auditory system. Asymmetries are affected by stimulus type, for example, hemispheric activation patterns have been shown to change from right to left cortex as stimuli change from speech to nonspeech. In addition, the presence of noise has differential effects on the contribution of the two hemispheres. Modifications of typical asymmetric cortical patterns occur when pathology is present, as in hearing loss or tinnitus. We show that in response to speech sounds, individuals with unilateral hearing loss lose the normal asymmetric pattern due to both a decrease in contralateral hemispheric activity and an increase in the ipsilateral hemisphere. These studies demonstrate the utility of modern neuroimaging techniques in functional investigations of the human auditory system. Neuroimaging techniques may provide additional insight as to how the cortical auditory pathways change with experience, including sound deprivation (e.g., hearing loss) and sound experience (e.g., training). Such investigations may explain why some populations appear to be more vulnerable to changes in hemispheric symmetry such as children with learning problems and the elderly.

Classification and Extraction of Resting State Networks Using Healthy and Epilepsy fMRI Data.

Functional magnetic resonance imaging studies have significantly expanded the field's understanding of functional brain activity of healthy and patient populations. Resting state (rs-) fMRI, which does not require subjects to perform a task, eliminating confounds of task difficulty, allows examination of neural activity and offers valuable functional mapping information. The purpose of this work was to develop an automatic resting state network (RSN) labeling method which offers value in clinical workflow during rs-fMRI mapping by organizing and quickly labeling spatial maps into functional networks. Here independent component analysis (ICA) and machine learning were applied to rs-fMRI data with the goal of developing a method for the clinically oriented task of extracting and classifying spatial maps into auditory, visual, default-mode, sensorimotor, and executive control RSNs from 23 epilepsy patients (and for general comparison, separately for 30 healthy subjects). ICA revealed distinct and consistent functional network components across patients and healthy subjects. Network classification was successful, achieving 88% accuracy for epilepsy patients with a naïve Bayes algorithm (and 90% accuracy for healthy subjects with a perceptron). The method's utility to researchers and clinicians is the provided RSN spatial maps and their functional labeling which offer complementary functional information to clinicians' expert interpretation.

Molecular characterization of two novel splice variants of G alphai2 in the rat vestibular periphery.

GTP binding proteins play an important role in mediating signals transduced across the cell membrane by membrane-bound receptors. We previously described a partial sequence, termed Galphai2vest, obtained from rat vestibular tissue that was nearly identical to rat Galphai2. Using an experimental strategy to further characterize Galphai2vest (GenBank accession number AF189020) and identify other possible Galphai2-related transcripts expressed in the rat vestibular periphery, we employed a RecA-based gene enrichment protocol in place of conventional library screening techniques. We identified two novel Galphai2 splice variants, Galphai2(a) (GenBank accession number AY899210) and Galphai2(b) (GenBank accession number AY899211), that have most of exons 8 and 9 deleted, and exons 5 through 9 deleted, respectively. In situ hybridization studies were completed to determine the differential expression of Galphai2 between the vestibular primary afferent neurons and the vestibular end organs. Computer modeling and predicted 3D conformation of the wild type Galphai2 and the two splice variants were completed to evaluate the changes associated with the Gbetagamma and GTP binding sites. These two novel alternatively spliced isoforms of Galphai2 putatively encode truncated proteins that could serve unique roles in the physiology of the vestibular neuroepithelium. Galphai2vest was found to be a processed pseudogene.

Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.

Electrophysiologic effects of placing cochlear implant electrodes in a perimodiolar position in young children.

OBJECTIVE: The purpose of this study was to intraoperatively record the electrically evoked auditory brainstem response (EABR) before and after placement of the electrode positioning system (EPS) (CII Bionic Ear with HiFocus I cochlear implant electrode array) as well as before and after stylet removal (Nucleus Contour cochlear implant electrode array). It was hypothesized that physiologic changes would occur after perimodiolar positioning of the electrode array and these changes would be evident from the EABR recordings. STUDY DESIGN: Consecutive young (11-36 month old) pediatric cochlear implant recipients (n = 17) had intraoperative EABRs recorded from three intracochlear electrodes that represented apical, medial, and basal locations. Wave V amplitudes and thresholds were studied relative to electrode location and pre- versus postperimodiolar positioning. These evoked potential measures were analyzed for statistical significance. SETTING: Tertiary referral children's hospital/medical college. RESULTS: Wave V thresholds of the EABR were lower, and amplitudes were larger after perimodiolar positioning, although the changes were dependent on electrode location and implant design. Statistically significant decreases in EABR wave V threshold and increases in suprathreshold wave V amplitude were found for the basal electrode for the CII Bionic Ear HiFocus I and for the apical electrode for the Nucleus Contour. CONCLUSIONS: Placement of either the CII Bionic Ear HiFocus I or Nucleus Contour cochlear implant electrode array in the perimodiolar position in young children resulted in less electrical current necessary to stimulate the auditory system. Changes in electrophysiologic thresholds and amplitudes, measured with EABR, indicate that the electrode array is placed closer to the modiolus with both electrode designs.

Auditory sensitivity in children using the auditory steady-state response.

OBJECTIVE: To determine the effectiveness of auditory steady-state response (ASSR) as a measure of hearing sensitivity in young children suspect for significant hearing loss. DESIGN: Within-subject comparisons of click auditory brainstem response (ABR) thresholds and ASSR thresholds. SUBJECTS: The study population comprised 42 children suspect for hearing loss and subsequently referred for hearing assessment using electrophysiologic techniques. MAIN OUTCOME MEASURES: Electrophysiologic threshold responses for click ABR and ASSR stimuli (0.5, 1, 2, and 4 kHz) for right and left ears. RESULTS: Based on ABR and ASSR thresholds, 50% of the subjects demonstrated significant hearing loss in the severe to profound range. In some subjects, ASSRs were present at higher stimulus levels when click ABRs were absent. Significant correlations (P<.05) were found between high-frequency ASSR and click ABR thresholds for this study sample. For some subjects, ASSR findings suggested differences between ears that were not observable from the no-response click ABR results. CONCLUSIONS: Auditory steady-state response testing may provide additional information for children who demonstrate hearing levels in the severe to profound range. This information may be helpful when selecting the ear for cochlear implantation for a young hearing-impaired child. Multiple objective methods, such as ABR and ASSR testing, may be needed to determine accurate hearing sensitivity for young children being considered for sensory devices, and in particular, cochlear implants.

Electrically evoked auditory brainstem responses in adults and children: effects of lateral to medial placement of the nucleus 24 contour electrode array.

OBJECTIVE: Previous electrophysiologic studies of electrode placement within the scala tympani in both animals and humans have shown effects on neural responses to electrical stimulation. The specific effects, however, may be dependent on electrode design, the location of an electrode along the array, and the method of perimodiolar positioning. The present study compares the effects of lateral and medial positioning of the Nucleus Contour electrode array on electrophysiologic responses in adult and pediatric subjects. STUDY DESIGN: Prospective clinical study. SETTING: Comprehensive Cochlear Implant Program/Tertiary Referral Center. PATIENTS: Subjects were adults (n = 15) and children (n = 20) who were consecutively implanted at our center with the Nucleus 24 Contour device. INTERVENTION: Rehabilitative. MAIN OUTCOME MEASURES: Intraoperative electrically evoked auditory brainstem responses (EABRs) were recorded within subjects for lateral and medial placement of the electrode array. Effects of electrode placement on EABR Wave V threshold and suprathreshold amplitude were measured. RESULTS: Group analyses showed significant decreases in EABR threshold and significant increases in EABR amplitude across all electrodes with medial electrode placement. The effects differed across electrode locations for the adult and pediatric subjects. No significant changes in Wave V input/output function slope were found. CONCLUSION: Medial electrode placement from stylet removal with the Nucleus 24 Contour array results in an increased neural response compared with the lateral condition as demonstrated by lower threshold and larger suprathreshold amplitude of the EABR. Possible clinical implications of these findings are lower psychophysical threshold and comfortable levels with medial cochlear electrode position.

Neuromagnetic source imaging of abnormal spontaneous activity in tinnitus patient modulated by electrical cortical stimulation.

Electrical cortical stimulation (CS) of the auditory cortices has been shown to reduce the severity of debilitating tinnitus in some patients. In this study, we performed MEG source imaging of spontaneous brain activity during concurrent CS of the left secondary auditory cortex of a volunteer suffering from right unilateral tinnitus. CS produced MEG artifacts which were successfully sorted and removed using a combination of sensor and source level signal separation and classification techniques. This contribution provides the first proof of concept reporting on analysis of MEG data with concurrent CS. Effects of CS on ongoing brain activity were revealed at the MEG sensor and source levels and indicate CS significantly reduced ongoing brain activity in the lower frequency range (<40Hz), and emphasized its higher (>40Hz), gamma range components. Further, our results show that CS increased the spectral correlation across multiple frequency bands in the low and high gamma ranges, and between the alpha and beta bands of the MEG. Finally, MEG sources localized in the auditory cortices and nearby regions exhibited abnormal spectral activity that was suppressed by CS. These results provide promising evidence in favor of the Thalamocortical Dysrhytmia (TCD) hypothesis of tinnitus, and suggest that CS may prove to be an effective treatment of tinnitus when targeted to brain regions exhibiting abnormal spontaneous activity.

The superior longitudinal fasciculus and speech arrest.

We present a 59-year-old woman with recurrent glioblastoma multiforme involving the left medial frontal and cingulate gyri. Diffusion tensor imaging (DTI) showed inferior-lateral tumor border proximity to the superior-medial (supracallosal) portion of the left frontal superior longitudinal fasciculus (SLF). Dissections of the tumor border contacting the dominant SLF caused speech arrests 8 times, with full recovery. At postoperative day 2, edema caused transient mild aphasia and paraphasic errors. Postoperative DTI showed an inferior-lateral resection cavity in immediate proximity to the supracallosal aspect of the left SLF. The case demonstrates excellent correlation between tumor border proximity to the dominant SLF shown at DTI and speech deficits caused by intraoperative dissections and postoperative edema. The case is the first to demonstrate speech arrest associated with lesion proximity to the supracallosal aspect of the SLF. Other SLF-related deficits are reviewed.

Electrically evoked auditory brain stem responses for lateral and medial placement of the Clarion HiFocus electrode.

OBJECTIVE: The purpose of this study was to compare the electrically evoked auditory brain stem response (EABR) for lateral and medial placement of the Clarion HiFocus cochlear implant electrode array via the electrode positioning system (EPS). DESIGN: Twenty-five adult and pediatric cochlear implant recipients participated in the study. Intraoperatively recorded EABRs were evoked by stimuli via three intracochlear electrodes representing apical, medial, and basal locations, and responses were elicited before and after positioner insertion. Evoked potential measures of wave V amplitude and threshold were examined for statistical significance using ANOVA for repeated measures and Chi-Square methods. RESULTS: For a given supra-threshold stimulus level, the increase in EABR wave V amplitude was significantly larger after EPS placement compared to before EPS placement for electrodes 1 (apical) and 13 (basal). Likewise, when the stimulus was decreased to obtain a minimal amplitude, the wave V threshold was significantly lower after EPS placement for electrodes 7 (medial) and 13. The number of measurements that showed decreased wave V threshold after EPS insertion was significantly dependent on intracochlear electrode location. CONCLUSIONS: Placement of the Clarion Electrode Positioning System following HiFocus electrode insertion resulted in a reduction in the electrical current required to activate the auditory system. The effect of the EPS was greatest for the basal location, demonstrated by lower wave V thresholds and a larger percentage increase in wave V amplitude. The EABR reflected electrophysiologic changes relative to lateral-to-medial changes in intracochlear electrode position due to the EPS.

Recognition of speech presented at soft to loud levels by adult cochlear implant recipients of three cochlear implant systems.

OBJECTIVE: The purpose of this study was to conduct a large-scale investigation with adult recipients of the Clarion, Med-El, and Nucleus cochlear implant systems to (1) determine average scores and ranges of performance for word and sentence stimuli presented at three intensity levels (70, 60, and 50 dB SPL); (2) provide information on the variability of scores for each subject by obtaining test-retest measures for all test conditions; and (3) further evaluate the potential use of lower speech presentation levels (i.e., 60 and/or 50 dB SPL) in cochlear implant candidacy assessment. DESIGN: Seventy-eight adult cochlear implant recipients, 26 with each of the three cochlear implant systems, participated in the study. To ensure that the data collected reflect the range of performance of adult recipients using recent technology for the three implant systems (Clarion HiFocus I or II, Med-El Combi 40+, Nucleus 24M or 24R), a composite range and distribution of consonant-nucleus-consonant (CNC) monosyllabic word scores was determined. Subjects using each device were selected to closely represent this range and distribution of CNC performance. During test sessions, subjects were administered the Hearing in Noise Test (HINT) sentence test and the CNC word test at three presentation levels (70, 60, and 50 dB SPL). HINT sentences also were administered at 60 dB SPL with a signal-to-noise ratio (SNR) of +8 dB. Warble tones were used to determine sound-field threshold levels from 250 to 4000 Hz. Test-retest measures were obtained for each of the speech recognition tests as well as for warble-tone sound-field thresholds. RESULTS: Cochlear implant recipients using the Clarion, Med-El, or Nucleus devices performed on average equally as well at 60 compared with 70 dB SPL when listening for words and sentences. Additionally, subjects had substantial open-set speech perception performance at the softer level of 50 dB SPL for the same stimuli; however, subjects' ability to understand speech was poorer when listening in noise to signals of greater intensity (60 dB SPL + 8 SNR) than when listening to signals presented at a soft presentation level (50 dB SPL) in quiet. A significant correlation was found between sound-field thresholds and speech recognition scores for presentation levels below 70 dB SPL. The results demonstrated a high test-retest reliability with cochlear implant users for these presentation levels and stimuli. Average sound-field thresholds were between 24 and 29 dB HL for frequencies of 250 to 4000 Hz, and results across sessions were essentially the same. CONCLUSIONS: Speech perception measures used with cochlear implant candidates and recipients should reflect the listening challenges that individuals encounter in natural communication situations. These data provide the basis for recommending new candidacy criteria based on speech recognition tests presented at 60 and/or 50 dB SPL, intensity levels that reflect real-life listening, rather than 70 dB SPL.