Charles J. Limb

Neural Substrates of Spontaneous Musical Performance: An fMRI Study of Jazz Improvisation

To investigate the neural substrates that underlie spontaneous musical performance, we examined improvisation in professional jazz pianists using functional MRI. By employing two paradigms that differed widely in musical complexity, we found that improvisation (compared to production of over-learned musical sequences) was consistently characterized by a dissociated pattern of activity in the prefrontal cortex: extensive deactivation of dorsolateral prefrontal and lateral orbital regions with focal activation of the medial prefrontal (frontal polar) cortex. Such a pattern may reflect a combination of psychological processes required for spontaneous improvisation, in which internally motivated, stimulus-independent behaviors unfold in the absence of central processes that typically mediate self-monitoring and conscious volitional control of ongoing performance. Changes in prefrontal activity during improvisation were accompanied by widespread activation of neocortical sensorimotor areas (that mediate the organization and execution of musical performance) as well as deactivation of limbic structures (that regulate motivation and emotional tone). This distributed neural pattern may provide a cognitive context that enables the emergence of spontaneous creative activity.

Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice.

The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer. Because of the diverse human disorders and organ systems affected by this gene, we developed an animal model by inactivating the murine Kvlqt1. No electrocardiographic abnormalities were observed. However, homozygous mice exhibited complete deafness, as well as circular movement and repetitive falling, suggesting imbalance. Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear. Surprisingly, homozygous mice also displayed threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia. Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.

Auditory function in patients with surgically treated superior semicircular canal dehiscence.

Objective: To characterize preoperative and postoperative audiologic findings in patients with superior semicircular canal dehiscence syndrome. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Patients with documented superior semicircular canal dehiscence syndrome (according to history, vestibular testing, and high-resolution computed tomography imaging) who underwent surgical repair of their dehiscence. Intervention: Middle fossa craniotomy for superior semicircular canal plugging and/or resurfacing. Main Outcome Measures: Audiologic testing both before and after surgery with pure-tone threshold measurements of air and bone conduction. Results: Twenty-nine subjects underwent surgical repair of superior semicircular canal dehiscence. Overall, there were no statistically significant differences by paired t test in hearing before or after surgery, in either air-conduction or bone-conduction thresholds, for 19 patients that had no previous surgical history. At least partial closure of air-bone gap was achieved in five patients. One patient with previous stapes surgery had significantly worse hearing both before and after canal repair compared with those without previous surgery. Two patients who had undergone previous middle fossa surgery with incomplete resolution of symptoms developed sensorineural hearing loss after revision surgery. Previous middle-ear exploration and tympanostomy tube placement did not seem to affect audiologic outcomes. Surgical hearing results did not differ according to method of canal repair (plugging versus resurfacing). Conclusion: Primary middle fossa repair of superior semicircular canal dehiscence is not associated with sensorineural hearing loss and, in some cases, can lead to normalization of conductive hearing loss. Revision middle fossa repair or previous stapes surgery may be associated with postoperative sensorineural hearing loss.

Development of Primary Axosomatic Endings in the Anteroventral Cochlear Nucleus of Mice

The endbulb of Held is a large synaptic ending that arises from the myelinated auditory nerve fibers. Endbulbs exhibit an elaborate pattern of terminal branching and produce extensive contact with the postsynaptic cell body. These structural features appear to underlie the tight coupling between presynaptic activity and postsynaptic spike discharges. As a first step toward understanding the relationship between environmental sounds and the development of these neural elements, we examined the age-related changes in the morphology of endbulbs of Held in CBA/J mice, a strain known to retain good hearing throughout life. Neurobiotin was injected into the modiolus of the cochlea in CBA/J mice ranging in age from postnatal day 1 to 7 months. Light microscopic analyses suggest that endbulbs of the CBA/J mice develop from small bouton endings at birth into large, highly branched structures in adults. This increase in structural complexity occurs mostly during the second through eighth postnatal weeks, and general stages of development can be defined. In addition, we compared endbulb structure between adult CBA/J mice and adult shaker-2 mice (Myo15sh2/sh2 ) and heterozygous littermates (Myo15+/sh2 ). The shaker-2 mouse carries a mutated myosin 15 gene that results in congenital deafness, presumably due to abnormally short stereocilia in hair cell receptors. Neurobiotin was injected into the modiolus of adult CBA/J, Myo15sh2/sh2 , and Myo15+/sh2 mice. Endbulbs of deaf adult Myo15sh2/sh2 mice exhibited a striking reduction in terminal branching compared with those of CBA/J and Myo15+/sh2 mice. Notably, the abnormal endbulbs of Myo15sh2/sh2 mice do not resemble immature endbulbs of normal-hearing mice, suggesting that deafness does not simply arrest development.

Predictors of Vestibular Schwannoma Growth and Clinical Implications

Objective: Vestibular schwannomas exhibit variable and unpredictable patterns of growth. We evaluated the extent to which tumor growth influences the management of these benign tumors, and we explored symptom markers present at diagnosis that may be predictive of tumor growth. Study Design: Retrospective case review. Setting: Tertiary care hospital center. Patients: One hundred eighty patients with unilateral vestibular schwannomas diagnosed between 1997 and 2007 who were initially managed conservatively by serial observation. Intervention(s): Serial observation versus eventual microsurgical or radiosurgical treatment. Main Outcome Measure(s): Tumor growth, defined as a 1 mm/year or greater increase in tumor size. Results: We observed that tumor growth was the most important predictor of a change in treatment strategy from serial observation to microsurgical or radiosurgical treatment. We further noted in multivariate analyses that larger tumor size at diagnosis was associated with higher odds of tumor growth, such that each 1-mm increment in tumor size at presentation increased the odds of growth by 20%. We also found that the symptom marker of tinnitus at diagnosis significantly increased the odds of tumor growth nearly 3-fold. Conclusion: Tumor growth plays a significant role in guiding the management of vestibular schwannomas. Assessment of tumor size at diagnosis and for the presence of tinnitus may allow for risk stratification of patients with newly diagnosed vestibular schwannomas and for a more rational application of the conservative management approach.

Radiosurgery of Glomus Jugulare Tumors: A Meta-analysis

PURPOSE During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors. METHODS AND MATERIALS To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data when Cochranes statistic was statistically insignificant and the inconsistency among studies was <25%. Bias was assessed using the Egger funnel plot test. RESULTS Across all studies, 97% of patients achieved tumor control, and 95% of patients achieved clinical control. Eight studies reported a mean or median follow-up time of >36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control. CONCLUSIONS The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.

Technological, biological, and acoustical constraints to music perception in cochlear implant users

Despite advances in technology, the ability to perceive music remains limited for many cochlear implant users. This paper reviews the technological, biological, and acoustical constraints that make music an especially challenging stimulus for cochlear implant users, while highlighting recent research efforts to overcome these shortcomings. The limitations of cochlear implant devices, which have been optimized for speech comprehension, become evident when applied to music, particularly with regards to inadequate spectral, fine-temporal, and dynamic range representation. Beyond the impoverished information transmitted by the device itself, both peripheral and central auditory nervous system deficits are seen in the presence of sensorineural hearing loss, such as auditory nerve degeneration and abnormal auditory cortex activation. These technological and biological constraints to effective music perception are further compounded by the complexity of the acoustical features of music itself that require the perceptual integration of varying rhythmic, melodic, harmonic, and timbral elements of sound. Cochlear implant users not only have difficulty perceiving spectral components individually (leading to fundamental disruptions in perception of pitch, melody, and harmony) but also display deficits with higher perceptual integration tasks required for music perception, such as auditory stream segregation. Despite these current limitations, focused musical training programs, new assessment methods, and improvements in the representation and transmission of the complex acoustical features of music through technological innovation offer the potential for significant advancements in cochlear implant-mediated music perception.

Pilot testing of an assessment tool for competency in mastoidectomy

To determine the feasibility, validity, and reliability of an evaluation tool for the assessment of competency in mastoid surgery. This study tests the hypothesis that residents of dissimilar training levels differ in their technical performance as measured by this tool.

Hearing outcomes after surgical plugging of the superior semicircular canal by a middle cranial fossa approach

Objective To determine postoperative hearing outcomes after surgical plugging via middle cranial fossa approach for superior semicircular canal dehiscence syndrome (SCDS). Study Design Clinical review. Setting Tertiary care medical center. Patients Forty-three cases of SCDS based on history, physical examination, vestibular function testing, and computed tomography imaging confirming the presence of a dehiscence. All patients underwent surgical plugging of the superior semicircular canal via middle cranial fossa approach. Intervention Pure tone audiometry was performed preoperatively and at 7 days and at least 1 month postoperatively. Main Outcome Measures Change in air-bone gap (ABG) and pure tone average (PTA). Results Preoperative average ABG across 0.25, 0.5, 1, and 2 kHz was 16.0 dB (standard deviation [SD], 7.5 dB). At 7 days postoperatively, average ABG was 16.5 dB (SD, 11.1; p = 0.42), and at greater than 1 month was 8.1 dB (SD, 8.4; p < 0.001). 53% (95% confidence interval, 33–69) of affected ears had greater than 10 dB increase in their 4-frequency (0.5, 1, 2, and 4 kHz) PTA measured by bone-conduction (BC) threshold 7 days postoperatively and 25% (95% confidence interval, 8–39) at greater than 1 month postoperatively. Mean BC PTA of affected ears was 8.4 dB hearing loss (HL) (SD, 10.4) preoperatively. Compared with baseline, this declined to 19.2 dB HL (SD, 12.6; p < 0.001) at 7 days postoperatively and 16.4 dB HL (SD, 18.8; p = 0.01) at greater than 1 month. No significant differences in speech discrimination score were noted (F = 0.17). Conclusion Low-frequency air-bone gap decreases after surgical plugging and seems to be due to both increased BC thresholds and decreased AC thresholds. Surgical plugging via a middle cranial fossa approach in SCDS is associated with mild high-frequency sensorineural hearing loss that persists in 25% but no change in speech discrimination.

Acoustic Neuromas after Failed Radiation Therapy: Challenges of Surgical Salvage

Objectives: As stereotactic radiation has emerged as a treatment option for acoustic neuromas, cases that require surgical salvage after unsuccessful radiation have emerged. We present a comparison of the technical challenges faced by the surgeons in the treatment of irradiated versus nonirradiated acoustic neuromas.