Steven W. Cheung

Reward-dependent plasticity in the primary auditory cortex of adult monkeys trained to discriminate temporally modulated signals

Adult owl monkeys were trained to detect an increase in the envelope frequency of a sinusoidally modulated 1-kHz tone. Detection was positively correlated with the magnitude of the change in the envelope frequency. Surprisingly, neuronal responses recorded in the primary auditory cortex of trained monkeys were globally suppressed by the modulated tone. However, the contrast in neuronal responsiveness to small increases versus large increases in envelope frequencies was actually enhanced in the trained animals. The results suggest behaviorally contingent inhibitory and excitatory processes that are modulated by the probability that a particular signal predicts a reward.

Lemierre's syndrome: two cases of postanginal sepsis.

Lemierres disease consists of suppurative thrombophlebitis of the IJV in the presence of oropharyngeal infection and can be complicated by septic pulmonary emboli. If a patient has an oropharyngeal or deep neck infection and neck pain suspicious for IJV thrombosis, a CT or MRI is warranted to establish the diagnosis. Blood cultures should be obtained to establish the responsible organism. In most cases F. necrophorum, an anaerobic bacterium, is responsible for the sepsis. Once the diagnosis of Lemierres disease is made, long-term, high-dose intravenous antibiotics with beta-lactamase anaerobic activity should be initiated. In cases with persistent sepsis and emboli despite appropriate medical management, ligation or excision of the IJV should be performed. Finally, if there is clinical or radiologic evidence of retrograde cavernous sinus thrombosis, the use of anticoagulants should be considered.

Descending projections to the inferior colliculus from the posterior thalamus and the auditory cortex in rat, cat, and monkey.

Projections from the posterior thalamus and medial geniculate body were labeled retrogradely with wheat germ agglutinin conjugated to horseradish peroxidase injected into the rat, cat, and squirrel monkey inferior colliculus. Neurons were found ipsilaterally in the (1) medial division of the medial geniculate body, (2) central gray, (3) posterior limitans nucleus, and the (4) reticular part of the substantia nigra. Bilateral projections involved the (5) peripeduncular/suprapeduncular nucleus, (6) subparafascicular and posterior intralaminar nuclei, (7) nucleus of the brachium of the inferior colliculus, (8) lateral tegmental/lateral mesencephalic areas, and (9) deep layers of the superior colliculus. The medial geniculate projection was concentrated in the caudal one-third of the thalamus; in contrast, the labeling in the subparafascicular nucleus, substantia nigra, and central gray continued much further rostrally. Robust anterograde labeling corresponded to known patterns of tectothalamic projection. Biotinylated dextran amine deposits in the rat inferior colliculus revealed that (1) many thalamotectal cells were elongated multipolar neurons with long, sparsely branched dendrites, resembling neurons in the posterior intralaminar system, and that other labeled cells were more typical of thalamic relay neurons; (2) some cells have reciprocal projections. Similar results were seen in the cat and squirrel monkey. The widespread origins of descending thalamic influences on the inferior colliculus may represent a phylogenetically ancient feedback system onto the acoustic tectum, one that predates the corticocollicular system and modulates nonauditory centers and brainstem autonomic nuclei. Besides their role in normal hearing such pathways may influence behaviors ranging from the startle reflex to the genesis of sound-induced seizures.

Epistaxis Originating From Traumatic Pseudoaneurysm of the Internal Carotid Artery: Diagnosis and Endovascular Therapy

Posttraumatic pseudoaneurysm of the internal carotid artery (ICA) is an uncommon but potentially fatal cause of epistaxis. Because the onset of delayed bleeding from the time of injury is variable, prompt diagnosis of cavernous ICA pseudoaneurysm is often a clinical challenge. The relative urgency to evaluate for this disease is highlighted by the morbid nature of this entity. Optimal management demands rapid recognition and treatment to give the best functional outcome. The authors present a case series of six patients with skull base ICA pseudoaneurysm. A unifying feature in the majority of patients is the development of delayed, massive epistaxis. The time course for presentation of delayed life‐threatening epistaxis ranged from 5 days to 9 weeks. Two patients exhibited the classic triad of unilateral blindness, orbital fractures, and massive epistaxis. All patients requiring intervention were successfully treated with endovascular embolization techniques that included detachable balloons and coils. The clinical and radiologic findings in this case series are presented. The relevant anatomy, diagnosis, and treatment of traumatic ICA pseudoaneurysm are reviewed. A contemporary treatment strategy is proposed.

Hearing preservation after stereotactic radiosurgery for vestibular schwannoma: A systematic review

Radiosurgery has evolved into an effective alternative to microsurgical resection in the treatment of patients with vestibular schwannoma. We performed a systematic analysis of the literature in English on the radiosurgical treatment of vestibular schwannoma patients. A total of 254 published studies reported assessable and quantifiable outcome data of patients undergoing radiosurgery for vestibular schwannomas. American Association of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A or B and Gardner-Robertson (GR) classification I or II were defined as having preserved hearing. A total of 5825 patients (74 articles) met our inclusion criteria. Practitioners who delivered an average dose of 12.5 Gy as the marginal dose reported having a higher hearing preservation rate (12.5 Gy=59% vs. >12.5 Gy=53%, p=0.0285). Age of the patient was not a significant prognostic factor for hearing preservation rates (<65 years=58% vs. >65 years=62%; p=0.4317). The average overall follow-up was 41.2 months. Our data suggest that an overall hearing preservation rate of about 57% can be expected after radiosurgical treatment, and patients treated with 12.5 Gy were more likely to have preserved hearing.

Auditory cortical neuron response differences under isoflurane versus pentobarbital anesthesia.

Response properties of the middle layers of feline primary auditory cortex neurons to simple sounds were compared for isoflurane versus pentobarbital anesthesia in a within subject study control design. Initial microelectrode recordings were made under isoflurane anesthesia. After a several hour washout period, recordings were repeated at spatially matched locations in the same animal under pentobarbital. The median spatial separation between matched recording locations was 50 microns. Excitatory frequency tuning curves (n=71 pairs) to tone bursts and entrainment to click train sequences (n=64 pairs) ranging from 2 to 38 Hz were measured. Characteristic frequency and BW10 and BW30 were not different under either anesthetic. The spontaneous rate was slightly decreased (P<0.05) for isoflurane (median 4.2 spikes/s) compared to pentobarbital (median 5.8 spikes/s). Minimum median threshold and latency were elevated by 12 dB and 2 ms, respectively, under isoflurane. Entrainment to click sequences assumed a lowpass filter profile under both anesthetics, but was markedly impoverished under isoflurane. Responses to click sequences under isoflurane were phasic to the first click but had very poor following to subsequent elements. Compared to pentobarbital, isoflurane appears to have a profound impact on response sensitivity and temporal response properties of auditory cortical neurons.

TINNITUS MODULATION BY DEEP BRAIN STIMULATION IN LOCUS OF CAUDATE NEURONS (AREA LC)

Tinnitus is an auditory disorder characterized by perception of internally generated phantom auditory sensations without corresponding mechanical stimuli arising from the body or external environment. Current auditory based treatment approaches, sometimes in conjunction with nonauditory based strategies, such as Tinnitus Retraining Therapy and Cognitive Behavioral Therapy, have been helpful in mitigating symptoms for the majority of patients. Yet there are over 1 million tinnitus sufferers who still endure troublesome chronic, continuous head noises that are debilitating and interfere with activities of daily living. Here we show that application of deep brain stimulation (DBS) therapy to a locus of caudate neurons (area LC) in the body of the nucleus, a subsite of the striatum that is not part of the classical auditory pathway, can decrease or increase tinnitus loudness perception. The DBS lead traversed through or was adjacent to area LC in six Parkinsons disease and essential tremor subjects with concomitant tinnitus who underwent implantation of the subthalamic or ventral intermediate nucleus. In five subjects where the DBS lead tip traversed area LC, tinnitus loudness in both ears was suppressed to a nadir of level 2 or lower on a 0-10 rating scale. In one subject where the DBS lead was outside area LC, tinnitus was not modulated. In three subjects with preoperative and postoperative audiograms, hearing thresholds were unchanged by area LC stimulation. Neuromodulation of area LC may be interrupting perceptual integration of phantom sensations generated in the central auditory system. This new, basal ganglia based approach to tinnitus modulation warrants further investigation and may be ultimately refined to treat patients with refractory symptoms.

Sensory representation abnormalities that parallel focal hand dystonia in a primate model.

In our hypothesis of focal dystonia, attended repetitive behaviors generate aberrant sensory representations. Those aberrant representations interfere with motor control. Abnormal motor control strengthens sensory abnormalities. The positive feedback loop reinforces the dystonic condition. Previous studies of primates with focal hand dystonia have demonstrated multi-digit or hairy-glabrous responses at single sites in area 3b, receptive fields that average ten times larger than normal, and high receptive field overlap as a function of horizontal distance. In this study, we strengthen and elaborate these findings. One animal was implanted with an array of microelectrodes that spanned the border between the face and digits. After the animal developed hand dystonia, responses in the initial hand representation increasingly responded to low threshold stimulation of the face in a columnar substitution. The hand-face border that is normally sharp became patchy and smeared over 1 mm of cortex within 6 weeks. Two more trained animals developed a focal hand dystonia variable in severity across the hand. Receptive field size, presence of multi-digit or hairy-glabrous receptive fields, and columnar overlap covaried with the animals ability to use specific digits. A fourth animal performed the same behaviors without developing dystonia. Many of its physiological measures were similar to the dystonic animals, but receptive field overlap functions were minimally abnormal, and no sites shared response properties that are normally segregated such as hairy-glabrous combined fields, or multi-digit fields. Thalamic mapping demonstrated proportionate levels of abnormality in thalamic representations as were found in cortical representations.

Beyond audiofacial morbidity after vestibular schwannoma surgery.

OBJECT Outcomes following vestibular schwannoma (VS) surgery have been extensively described; however, complication rates reported in the literature vary markedly. In addition, the majority of reports have focused on outcomes related to cranial nerves (CNs) VII and VIII. The objective of this study was to analyze reported morbidity unrelated to CNs VII and VIII following the resection of VS. METHODS The authors performed a comprehensive search of the English language literature, identifying and aggregating morbidity and death data from patients who had undergone microsurgical removal of VSs. A subgroup analysis based on surgical approach and tumor size was performed to compare rates of CSF leakage, vascular injury, neurological deficit, and postoperative infection. RESULTS One hundred articles met the inclusion criteria, providing data for 32,870 patients. The overall mortality rate was 0.2% (95% CI 0.1-0.3%). Twenty-two percent of patients (95% CI 21-23%) experienced at least 1 surgically attributable complication unrelated to CNs VII or VIII. Cerebrospinal fluid leakage occurred in 8.5% of patients (95% CI 6.9-10.0%). This rate was markedly increased with the translabyrinthine approach but was not affected by tumor size. Vascular complications, such as ischemic injury or hemorrhage, occurred in 1% of patients (95% CI 0.75-1.2%). Neurological complications occurred in 8.6% of cases (95% CI 7.9-9.3%) and were less likely with the resection of smaller tumors (p < 0.0001) and the use of the translabyrinthine approach (p < 0.0001). Infections occurred in 3.8% of cases (95% CI 3.4-4.3%), and 78% of these infections were meningitis. CONCLUSIONS This study provides statistically powerful data for practitioners to advise patients about the published risks of surgery for VS unrelated to compromised CNs VII and VIII.

Plasticity in Primary Auditory Cortex of Monkeys with Altered Vocal Production

Response properties of primary auditory cortical neurons in the adult common marmoset monkey (Callithrix jacchus) were modified by extensive exposure to altered vocalizations that were self-generated and rehearsed frequently. A laryngeal apparatus modification procedure permanently lowered the frequency content of the native twitter call, a complex communication vocalization consisting of a series of frequency modulation (FM) sweeps. Monkeys vocalized shortly after this procedure and maintained voicing efforts until physiological evaluation 5-15 months later. The altered twitter calls improved over time, with FM sweeps approaching but never reaching the normal spectral range. Neurons with characteristic frequencies <4.3 kHz that had been weakly activated by native twitter calls were recruited to encode self-uttered altered twitter vocalizations. These neurons showed a decrease in response magnitude and an increase in temporal dispersion of response timing to twitter call and parametric FM stimuli but a normal response profile to pure tone stimuli. Tonotopic maps in voice-modified monkeys were not distorted. These findings suggest a previously unrecognized form of cortical plasticity that is specific to higher-order processes involved in the discrimination of more complex sounds, such as species-specific vocalizations.