Computational physiology of the neural networks of the primate globus pallidus: function and dysfunction.

The dorsal pallidal complex is made up of the external and internal segments of the globus pallidus (GPe and GPi respectively). It is part of the main axis of the basal ganglia (BG) that connects the thalamo-cortical networks to the BG input stages (striatum and subthalamic nucleus) and continues directly, and indirectly through the GPe, to the BG output stages (GPi and substantia nigra reticulata). Here we review the unique anatomical and physiological features of the pallidal complex and argue that they support the main computational goal of the BG main axis (actor); namely, a behavioral policy that maximizes future cumulative gains and minimizes costs. The three mono-layer competitive networks of the BG main axis flexibly extract relevant features from the current state of the thalamo-cortical activity to control current (ongoing) and future actions. We hypothesize that the striatal and the subthalamic projections neurons act as mono-stable integrators (class I excitability) and the in-vivo pallidal neurons act as bi-stable resonators (class II excitability). GPe neurons exhibit pausing behavior because their membrane potential lingers in the vicinity of an unstable equilibrium point and bi-stability, and these pauses enable a less-greedy exploratory behavioral policy. Finally, degeneration of midbrain dopaminergic neurons and striatal dopamine depletion (as in Parkinson's disease) lead to augmentation of striatal excitability and competitive dynamics. As a consequence the pallidal network, whose elements tend to synchronize as a result of their bi-stable resonance behavior, shifts from a Poissonian-like non-correlated to synchronous oscillatory discharge mode.

Spontaneous firing and evoked pauses in the tonically active cholinergic interneurons of the striatum.

The tonically active neurons (TANs) are a population of neurons scattered sparsely throughout the striatum that show intriguing patterns of firing activity during reinforcement learning. Following repeated pairings of a neutral stimulus with a primary reward, TANs develop a transient cessation of firing activity in response to the stimulus, termed the "conditioned pause response." In tasks where specific cues are arranged to signal the probability of particular outcomes, the pause response to both cue and outcome may differ in ways that suggest the involvement of different inputs to the same neuron. Here we review the cellular properties of cholinergic interneurons and describe the response to their afferents in terms of inducing TAN-like pauses in tonic firing. Recent work has shown that thalamostriatal inputs to cholinergic neurons transiently suppress firing activity via dopamine release. Because these pauses are initiated by subcortical pathways with limited sensory processing abilities, we propose that they are an ideal correlate for the pauses observed in TANs in response to cues signaling trial initiation. On the other hand, pauses that accompany outcome presentation contain higher-level information, including an apparent sensitivity to reward prediction error. Thus, these pauses may be mediated by cortical inputs to cholinergic interneurons. Although there is evidence linking cholinergic pauses to synaptic plasticity, much remains to be discovered about the effect of this relatively sparse but influential population on the striatal learning system.

Cortico-cerebellar coherence and causal connectivity during slow-wave activity.

Cerebral cortical slow-wave activity (SWA) is prominent during sleep and also during ketamine-induced anesthesia. SWA in electroencephalogram (EEG) recordings is closely linked to prominent fluctuations between up- and down-states in the membrane potential of pyramidal neurons. However, little is known about how the cerebellum is linked into SWA and whether slow cortical oscillations influence sensory cerebellar responses. To examine these issues, we simultaneously recorded EEG activity from the cerebral cortex (SI, MI, and supplementary motor area (SMA)), local field potentials at the input stage of cerebellar processing in the cerebellar granule cell layer (GCL) and inferior olive (IO), and single unit activity at the output stage of the cerebellum in the deep cerebellar nuclei (DCN). We found that in ketamine-anesthetized rats, SWA was synchronized between all recorded cortical areas and was phase locked with local field potentials of the GCL, IO and single unit activity in the DCN. We also found that cortical up-states are linked to activation of GCL neurons but to inhibition of cerebellar output from the DCN, with the latter an effect likely mediated by Purkinje cells. A partial coherence analysis showed further that a large portion of SWA shared between GCL and DCN was transmitted from the cortex, since the coherence shared between GCL and DCN was diminished when the effect of cortical activity was subtracted. To determine the causal flow of information between structures, a directed transfer function was calculated between the simultaneous activities of SI, MI, SMA, GCL and DCN. This analysis demonstrated that the primary direction of information flow was from cortex to the cerebellum and that SI had a stronger influence than other cortical areas on DCN activity. The strong functional connectivity with SI in particular is in agreement with previous findings of a strong cortical component in cerebellar sensory responses.

Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation.

Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)-lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.

Surgical management of large rotator cuff tears combined with instability in elite rugby football players.

Large rotator cuff tears are extremely uncommon in young people and when they occur they may be associated with shoulder instability. This paper reports on a series of six elite rugby union and rugby league footballers who presented with shoulder instability and large rotator cuff tears. They were treated with a two stage procedure: an open rotator cuff repair followed by an open shoulder stabilisation some 10 weeks later. All had successful outcomes. The paper also highlights the risk of tearing the rotator cuff when a patient continues to play contact sport with an untreated unstable shoulder.

Salvaging unstable or recurrent dislocating total hip arthroplasty with the constrained acetabular component.

PURPOSE: To review cases of implantation of constraining acetabular components for unstable or recurrent dislocating total hip arthroplasty at the Department of Orthopaedics, Concord Hospital, Sydney. METHODS: A retrospective analysis was performed on prospectively collected data of 13 consecutively enrolled patients. RESULTS: From 1989 to 2000, 13 constraining acetabular components were implanted into 13 patients as a revision procedure. The surgical approach for the implantation of the constrained liner was posterolateral in 11 cases; a modified Hardinge approach was applied in 2 cases. The mean clinical follow-up duration was 43 months (range, 14-121 months) and the mean age at the time of surgery was 73 years (range, 52-84 years). No patients were lost to follow-up. Indications for using the constrained acetabular component were recurrent dislocation in revision hip replacements (n=8), and intra-operative instability (n=5). There were no episodes of dislocation of the constrained arthroplasty. In 7 cases, the constrained component was implanted into a previously well-fixed shell. CONCLUSION: We recommend the judicious use of the constrained component in cases of hip instability during or after total hip arthroplasty when other methods are not successful.

Total hip arthroplasty for arthrodesed hips.

The benefits of converting an ankylosed or arthrodesed hip to total hip arthroplasty have been reported in the literature as have the technical difficulties associated with this procedure. This review, however, outlines the experience of a single surgeon (WJMB) at a single institution using uncemented prostheses. Between November 1991 and June 1996, 5 arthrodesed hips underwent uncemented total hip arthroplasty in 4 males and 1 female. Clinical and radiological follow-up review was for at least three years in all patients. In general, patients were satisfied with the outcome of their surgery with Harris Hip scores improving from an average of 62 preoperatively to an average of 72 postoperatively. The surgical outcome in these difficult cases was not as satisfactory as for routine total hip arthroplasty. Meticulous preoperative planning is required to aim toward leg length restoration and restoration of the abductor moment arm. A modular prosthesis allows versatility at surgery.

Anatomic variance of the coracoclavicular ligaments.

The coracoclavicular ligaments vary widely in morphology and anatomic descriptions. Few authors have adequately described the coracoclavicular ligaments' anatomy, and a number of discrepancies exist in the anatomy literature. This study examines the complex anatomy of the coracoclavicular ligaments and their relationships to clinically important bony landmarks. The geometric dimensions of 24 coracoclavicular ligament specimens from fresh human cadaveric shoulders were examined and quantified with 13 different measurements. Particular attention was given to any inter-specimen anatomic variance. The coracoid insertions of the conoid ligaments displayed high variance, with 33% (8/24) being confluent with the lateral fibers of the superior transverse scapular ligament. A further 15% (3/24) presented an additional lateral fascicle. The distance from the lateral trapezoid ligament to the distal clavicle averaged 15.3 mm. Three distinct and previously unreported conoid ligament variants lend themselves to an anatomic classification (types I, II, and III). A safety margin of 15 mm is suggested for distal clavicle resection in incomplete acromioclavicular joint injuries to preserve the intact coracoclavicular ligament.

Synchrony of rest tremor in multiple limbs in parkinson's disease: evidence for multiple oscillators.

Recent evidence points to involvement of central nervous system oscillators in Parkinson's disease (PD) rest tremor. It remains unknown whether one or multiple oscillators cause tremor in multiple limbs. Based on the prediction that multiple oscillators would cause low coherence even with similar average frequency, we studied 22 PD patients using accelerometers on multiple limbs. Records were digitized and spectral analysis was performed. Peak frequencies in the arms, legs, and chin were similar, indicating that biomechanical factors did not determine the frequency. Coherence between different axes of individual accelerometers and between different segments of the same limb was high. However, coherence between tremor in different limbs was low. There was no consistent pattern across patients of ipsi- vs. contralateral predominance of coherence. These data suggest that tremor in PD is generated by multiple oscillatory circuits, which operate on similar frequencies.

A new technique of subtrochanteric shortening in total hip arthroplasty: surgical technique and results of 9 cases.

Total hip arthroplasty for severe chronic proximal femoral migration, most commonly seen in congenital dislocation of the hip, has been associated with high rates of complications. A new technique of femoral subtrochanteric shortening osteotomy with the prosthesis in situ is described. This technique minimizes the potential complications, allows for correction of severe femoral neck anteversion, and gives excellent rotational stability, while preserving the proximal femur for better press-fit cementless fixation. In this series, there were 9 cases: 6 women and 2 men with a mean age of 53 years (range, 26-77 years). The average follow-up period was 56 months (range, 6-86 months). The mean preoperative Harris Hip Score was 31 (range, 20-35), and the mean postoperative score was 81 (range, 60-98). At follow-up, all patients reported significant pain relief and functional improvement. All osteotomies appeared to be healed on radiographs by 12 weeks. There were 3 complications. The first complication was a recurrent dislocation resulting from muscle incompetence, which was revised using a constrained liner and a 32-mm head with no further dislocations. The second complication was a breach of the femoral shaft, which was treated operatively using a longer stem. The third complication was a proximal femoral shaft split, which was treated by leaving the cerclage wire in situ. This technique should be considered in cases of congenital dislocation of the hip and when femoral shortening is needed.

Structural properties of the intact and the reconstructed coracoclavicular ligament complex.

Numerous procedures have been described for the operative management of acromioclavicular joint injuries, but surprisingly little information is available on the ultimate mechanical behavior of the native coracoclavicular ligament complex or on the various methods of reconstruction. We tested 19 fresh-frozen cadaveric bone-ligament-bone preparations of the coracoclavicular ligament in uniaxial tension at 25 mm/min until failure. Seven specimens were left intact, six had the trapezoid ligament sectioned, and six had the conoid ligament sectioned. Reconstruction of the coracoclavicular ligament was achieved using coracoacromial ligament transfers, woven polyester slings, suture anchors, and Bosworth screws; all reconstructions were also tested to failure. The intact coracoclavicular ligament failed by avulsion or midsubstance tear at 500 (+/-134) N, with a stiffness of 103 (+/-30) N/mm and elongation to failure of 7.7 (+/-1.9) mm. There was no significant difference between the contributions of the conoid or trapezoid ligaments in this loading configuration. Coracoclavicular slings and suture anchors provided strength similar to that of the coracoclavicular ligament, but with significantly greater deformations (14 to 26 mm). Screw fixation resulted in comparable stiffness and superior strength to the coracoclavicular ligament, but only if bicortical purchase was obtained. Coracoacromial ligament transfers were the weakest and least stiff, and augmentation with another form of coracoclavicular fixation is recommended. These results provide a useful baseline for comparison of the initial performance of reconstructive techniques with the performance of the native coracoclavicular ligament.

Potential role of doppler perfusion index in selection of patients with colorectal cancer for adjuvant chemotherapy.

BACKGROUND: As yet there is no established method of accurately identifying patients with colorectal cancer who, despite undergoing apparently curative resection, are at high risk of recurrence. We assessed whether the doppler perfusion index (DPI; ratio of hepatic arterial to total liver blood flow) could be used to select patients who should receive adjuvant chemotherapy. METHODS: We studied 120 patients undergoing curative surgery for colorectal cancer. DPI was measured before surgery with colour duplex doppler ultrasonography. A DPI value of at least 0.3 was defined as abnormal. All patients were followed up until death or for at least 5 years. RESULTS: At 5 years, patients with Dukes' stage A or B tumours (n=61) had recurrence-free survival of 57% and overall survival of 64%, compared with 39% and 42% for patients with Dukes' stage C tumours (n=59; p=0.016 and p=0.008, respectively). 47 patients had normal DPI values and 73 patients had abnormal values. Patients with normal DPI had recurrence-free survival of 89% and overall survival of 91%, compared with 22% and 29% for those with abnormal DPI values (both p<0.0001). CONCLUSIONS: DPI can be used to identify patients with colorectal cancer at high risk of recurrence who are in need of adjuvant treatment. However, further studies with larger numbers of patients are needed to confirm these findings.

A novel approach for assessing the quality and effectiveness of IACUC oversight in investigator compliance.

In research facilities that are registered with the U.S. Department of Agriculture (USDA), funded by the Public Health Service, or accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) International, the Institutional Animal Care and Use Committee (IACUC) is charged with oversight and evaluation of animal care and use under the terms of the Animal Welfare Act and the Guide for the Care and Use of Laboratory Animals. Although the committee's oversight of investigator compliance may be evaluated annually during USDA inspections and triennially during AAALAC International site visits, routinely assessing the quality and effectiveness of the IACUC's performance is difficult. To measure the successfulness of IACUC oversight, our committee retained a management consultant to objectively design and conduct a confidential survey that could be used to determine how the IACUC could improve the process of facilitating researcher compliance with federal regulations and accreditation standards. The consultant based the content of the survey on confidential interviews with all IACUC members, the IACUC administrator, and a cross sectional representation of the key animal-user population at the facility. The survey was then distributed to the entire animal-user population. Vice-presidents, directors, principal investigators, and technicians were included in the distribution. With a response rate of 34%, the survey results indicated that the facilitation process warranted refinements. The consultant provided the IACUC with its recommendations, which were based on the discernible trending information indicated in the survey responses. The IACUC developed a specific plan of action to address the consultant's recommendations and intends to re-survey the animal-user population once the action plan has been fully implemented. In summary, the survey is an excellent way to assess the quality and effectiveness of IACUC oversight in investigator compliance by determining the level of researcher satisfaction. The evaluation, review, and follow-up process using a confidential interview and questionnaire technique can enhance the performance and effectiveness of IACUC oversight.

Reinforcement-driven dimensionality reduction--a model for information processing in the basal ganglia.

Although anatomical studies of the basal ganglia show the existence of extensive convergence and lateral inhibitory connections, physiological studies failed to show correlated neural activity or lateral interaction in these nuclei. These seemingly contradictory results could be explained with a model in which the basal ganglia reduce the dimensionality of cortical information using optimal extraction methods. Simulations of this model predict a transient change in the efficacy of the feed-forward and lateral synapses following changes in reinforcement signal, causing an increase in correlated firing rates. This process ultimately restores the steady-state situation with diminished efficacy of lateral inhibition and no correlation of firing. Our experimental results confirm the model's predictions: rate correlations show a drastic decrease between the input stage (cortex) and output stage (pallidum). Moreover, preliminary analysis revealed that pallidal correlations show a transient increase following discrepancies between the animal's predictions and reality. We therefore propose that by using a reinforcement-driven dimensionality reduction process the basal ganglia achieve efficient extraction of cortical salient information that may then be used by the frontal cortex for execution and planning of forthcoming actions.

Exposure in difficult total knee arthroplasty using coronal tibial tubercle osteotomy.

Exposure in a total knee arthroplasty can be challenging regardless of whether it is a difficult primary or a revision. Various techniques both proximal and distal to the patella have been described and implemented to gain exposure and improve knee flexion. When patella eversion is not possible due to previous surgery or severe preoperative knee flexion contracture, a coronal tibial tubercle osteotomy may be utilized. We present successful results utilizing the coronal tibial tubercle osteotomy procedure. The technique involved in this series is based on that described by Whiteside. It involves the development of a long lateral musculoperiosteal flap incorporating the tibial tubercle and anterior tibia, and leaving the proximal tibial cortex intact. This is extended along the tibia distally for 10 cm. It finishes by gradually osteotomising the anterior surface of the tibial crest. The tubercle is reattached with wires at the end of the procedure. This technique minimizes complications that have been associated with the tibial tubercle osteotomy. The 10 knees in 9 patients, who had total knee arthroplasty with a coronal tibial tubercle osteotomy, were reviewed pre and postoperatively. All knees were assessed using the Hospital for Special Surgery knee score (HSS). The scores averaged 43.6 preoperatively (range, 29 57) and 79.2 postoperatively (range, 67 90), and the mean range of motion was 59.5 degrees preoperatively and 78.0 degrees postoperatively. There were no cases of extension lag. Fixed flexion deformity was present in 3 cases postoperatively. Average time to union at the proximal and distal ends of the osteotomy was 8 and 24 weeks respectively. There was no evidence of nonunion and no other significant complications occurred.

Flexor tendon lengthening in zone II injuries.

Primary repair of acute severed flexor tendons in zone II has replaced the "no-man's-land" concept, which advocates secondary procedures. Primary repair can be difficult when there are severe soft-tissue and bony injuries, and may lead to unfavorable results. The authors describe a technique that is simple, quick, and safe, and eliminates the need for tendon harvesting or other secondary procedures. It can also be used when a flexor profundus tendon gap occurs due to the injury.

Between passion and policy: litigating the Guckenberger case.

This article describes the Guckenberger lawsuit from the perspective of the attorneys who litigated the case on behalf of Boston University. It first discusses the events leading to the lawsuit, including then-Provost Jon Westling's speeches, his articulation of new policies regarding documentation for accommodations requests, and the university's refusal to allow course substitutions for required foreign language courses. The article then describes the main events in the lawsuit that resulted from those policy changes, focusing first on pretrial matters, such as the university's search for experts, the various motions filed prior to trial, and tactical issues. Moving to the trial itself, the article discusses the nature of the witness and expert testimony presented to the court and touches on the differences of opinion expressed at trial by experts in the field of learning disabilities. Finally, the article sets forth the court's ruling on the major issues in the case and reflects on the case's impact on institutions of higher education.

Biomechanical performance of Bankart repairs in a human cadaveric shoulder model.

The objective of this study was to develop a method to evaluate the biomechanical performance of Bankart repairs in a human cadaveric shoulder in a clinically relevant orientation. Twenty fresh-frozen human cadaveric shoulder girdles were used to compare the biomechanical performance of intact anteroinferior capsulolabral complexes with the biomechanical performance of three Bankart lesion reconstruction techniques. Repairs were performed on surgically created Bankart lesions. Evaluations were performed with the shoulders in glenohumeral abduction and external rotation. The repair techniques employed interosseous sutures, Mitek GII suture anchors, or Acufex T-Fix devices. The suture material used in all repairs was No. 2 Ti-Cron. The biomechanical performance of the three reconstruction techniques did not differ, but each was significantly inferior compared with that of the intact shoulder samples. The interosseous repairs failed by suture pullout through soft tissue. Repairs in the Mitek GII group failed by pullout of the suture anchors, suture breakage, or pullout of the suture through soft tissue. Repairs in the T-Fix group failed by pullout of the suture through soft tissue or failure of the polymer portion of the T-Fix suture.

Type 2 fractures of the distal clavicle: a new surgical technique.

Neer type 2 fractures of the distal clavicle have a high rate of nonunion and delayed union. In this series nine cases of coracoclavicular ligament reconstruction with Dacron graft material led to union at the fracture site. All patients had no symptoms and returned to full activity. This technique allows for stable fixation with early mobilization and return to work and sports.

Restoration of sensation in paraplegia by a sensory innervated plantar fillet free flap. Case report.

Sensory denervation most likely is the key factor to the multiple physiological derangements that predispose paraplegic patients to recurrent decubitus ulceration. A sensory innervated plantar free flap offers the ability to provide soft tissue coverage and to regain sensory innervation of the ulcer prone area in patients with recurrent ulceration. We present a patient in which an innervated plantar free flap was used to restore sensation to the sacral area in a patient with recurrent ulceration.