The effect of pain on involuntary and voluntary capture of attention.

BACKGROUND: There is converging evidence for the notion that pain affects a broad range of attentional domains. This study investigated the influence of pain on the involuntary capture of attention as indexed by the P3a component in the event-related potential derived from the electroencephalogram. METHODS: Participants performed in an auditory oddball task in a pain-free and a pain condition during which they submerged a hand in cold water. Novel, infrequent and unexpected auditory stimuli were presented randomly in a series of frequent standard and infrequent target tones. P3a and P3b amplitudes were observed to novel, unexpected and target-related stimuli, respectively. RESULTS: Both electrophysiological components were characterized by reduced amplitudes in the pain compared with the pain-free condition. Hit rate and reaction time to target stimuli did not differ between the two conditions presumably because the experimental task was not difficult enough to exceed attentional capacities under pain conditions. CONCLUSIONS: These results indicate that voluntary attention serving the maintenance and control of ongoing information processing (reflected by the P3b amplitude) is impaired by pain. In addition, the involuntary capture of attention and orientation to novel, unexpected information (measured by the P3a) is also impaired by pain. Thus, neurophysiological measures examined in this study support the theoretical positions proposing that pain can reduce attentional processing capacity. These findings have potentially important implications at the theoretical level for our understanding of the interplay of pain and cognition, and at the therapeutic level for the clinical treatment of individuals experiencing ongoing pain.

Pathway and hemispheric differences in the event-related potential (ERP) to monaural stimulation: a comparison of schizophrenic patients with normal controls.

Previous research has established the stability of the contralateral dominance effect of the auditory temporal N120 peak amplitude. The purpose of this experiment was to examine event-related potential (ERP) asymmetries in schizophrenia, with particular reference to this contralateral dominance phenomenon. Ten unmedicated schizophrenic patients and ten controls heard a series of monaural tones, with no task requirements, while EEG was recorded from Cz, Pz, T3, and T4 referred to linked earlobes. Patients were characterized by smaller N120 amplitudes than controls, an effect that was slightly more pronounced at temporal sites. Patients failed to show the normal N120 contralateral dominance effect. Hemisphere asymmetry ratios revealed that 50% of the patients showed ipsilateral dominance in the auditory pathways. Furthermore, the hemisphere asymmetries (whether ipsilaterally or contralaterally dominant) seen in patients were significantly greater than for controls. These data offer a new level of explanation for schizophrenic performance abnormalities in dichotic listening paradigms and an explanation for for the apparent dichotomy in patient performance between exaggerated right ear advantage (REA) and left ear advantage (LEA).

An event-related brain potential study of receptive speech comprehension using a modified Token Test.

There is a long and distinguished history of evaluating sensory functions with evoked potentials (EPs). However, the clinical utility of event-related brain potentials (ERPs) in the assessment of cognitive functions remains to be established. We present evidence for the efficacy of ERPs in the assessment of speech comprehension. In this normative study, a version of the Token Test (Boller and Vignolo, 1966, Brain, 89, 815-831: De Renzi and Vignolo, 1962, Brain, 85, 665-678) was modified for computer presentation with simultaneous ERP recordings and then administered to a group of healthy individuals (n = 27). A differential neural response pattern to incorrect and correct test items was obtained for the group and, more importantly, this result was also observed reliably at the individual subject level. This research complements on-going efforts in our laboratory to develop innovative measures for patients that are difficult or impossible to assess due to motoric and/or communicative limitations.

Effects of oxazepam and lorazepam on implicit and explicit memory: evidence for possible influences of time course.

The effects of oxazepam (30 mg), lorazepam (2 mg), and placebo on implicit and explicit memory were studied in two testing cycles, 100 and 170 min after drug administration. Thirty healthy volunteers were randomly assigned to one of three groups (placebo, oxazepam, or lorazepam) in a double-blind, independent groups design. Drug groups were equivalent prior to drug administration on a variety of cognitive measures. Following drug administration, both oxazepam and lorazepam equally impaired performance on a cued-recall explicit memory task relative to placebo, at both testing cycles. Relative to placebo, lorazepam markedly impaired priming on a word-stem completion implicit memory task, at both testing cycles. Consistent with previous work, oxazepam failed to produce impairments in priming on the word-stem completion task at 100 min post-drug administration. However, oxazepam was found significantly to impair priming on this latter task relative to placebo, at close to theoretical peak plasma concentration (i.e., 170 min post-drug administration). Explanations for the observed detrimental effect of oxazepam on implicit memory task performance are considered, including: possible time-dependent effects related to the relative rate of absorption of these two benzodiazepines (BZs); and potential contamination of the implicit memory task by explicit memory strategies during the second testing cycle.

Phonological aspects of word recognition as revealed by high-resolution spatio-temporal brain mapping.

We describe, for the first time, the use of high-resolution event-related brain potentials (hrERP) to identify the spatio-temporal characteristics of neural systems involved in phonological analysis. Subjects studied a visual word/non-word that was followed by the brief presentation of a prime letter (e.g. House, M) with the instruction to anticipate the word/non-word formed by replacing the word's first letter with the prime letter. After the prime letter, an auditory target word/non-word was presented that either matched/mismatched expectations (e.g., Mouse/Barn). ERPs were recorded to the onset of the auditory targets and scalp topographical maps were derived for the phonological mismatch negativity (PMN). The PMN reflected phonological analysis and examination of the peak topography revealed that the response was characterized by a prominent frontal, right-asymmetrical distribution. Spatial de-blurring (using current source density maps) indicated that the PMN scalp topography resulted primarily from an active left anterior source. The current results provide the initial evidence for the localization of the intra-cranial generator(s) involved in phonological analysis.

Latency shifts in the N2b component track phonological deviations in spoken words.

OBJECTIVE: We investigated event-related brain potentials (ERPs) elicited by a novel speech comprehension paradigm modelled after the neuropsychological Token Test. The objective of the study was to determine whether the ERPs were sensitive to differences in the initial phonemes of the speech stimuli. METHODS: Twenty-seven healthy subjects identified incorrect spoken sentences on the computerised Token Test (CTT). The incorrect spoken sentences contained one word that did not match the previously studied animations. The initial phonemes of these words were either different than or similar to the initial phonemes of their correct counterparts. RESULTS: Different initial phonemes were associated with an early N2b, while words having similar initial phonemes resulted in a substantially delayed N2b. CONCLUSION: The delayed latency effect was due to whether the incorrect word's initial phoneme matched or mismatched that of the expected word. In both cases, this component reflected a mismatch with an existing cognitive template maintained in phonological working memory. The results indicate that this mismatching effect reflected primarily attentional detection rather than language processing.

The disruptive effect of chronic pain on mismatch negativity.

OBJECTIVE: To investigate the effect of chronic pain on processes that generate the mismatch negativity (MMN). METHODS: Twelve participants with a diagnosis of chronic intractable pain were tested before and after pain treatment. During testing, event-related potentials were recorded while participants performed tasks of varying difficulty. RESULTS: The amplitude of the MMN was found to be greater following a nerve block procedure compared to MMN amplitude when participants were experiencing chronic pain. This effect was found to occur in the MMN for difficult-to-detect tones elicited while participants were performing a simultaneous cognitively demanding visual task. MMN amplitude was found to be greater with attention to difficult-to-detect deviants during pain but not in no pain conditions. CONCLUSIONS: These results provide an electrophysiological correlate of previous findings that high levels of pain disrupt cognition during the performance of demanding tasks.

Hemispheric lateralization in preattentive processing of speech sounds.

Event-related magnetoencephalographic (MEG) responses to infrequently presented spoken deviant syllables [di] and [ba] among repetitive standard [da)]syllables were recorded in subjects who either attended to these stimuli in order to discriminate the [ba] syllables or ignored them while attending a silent movie. In both conditions, the deviant syllables elicited a mismatch response (MMNm, the magnetic counterpart of mismatch negativity), which was stronger in the left than in the right auditory cortex, indicating left-hemispheric dominance in speech processing already at a preattentive processing level.

Pulsing direct current-induced repair of articular cartilage in rabbit osteochondral defects.

Osteochondral defects in the distal femoral condyles of rabbits exposed to a pulsing direct current exhibits an enhanced quality of repair. The signal, with a peak value of 2 microA repeating at 100 Hz, imposed an electric field in the tissue of 20-60 mV/cm2. Maximum efficacy was seen with a shorter period of exposure (40 vs. 160 h) initiated 48 h after surgery for 4 h/day. Repair tissue originated primarily from metaplasia of subchondral elements although hyperplasia of pre-existing chondrocytes at the margins of the defect could be detected. Defects in treated joints contained Safranin O staining material that was histologically similar to a disorganized hyaline cartilage. Central areas of the defects in control animals contained Safranin O-negative material that generally extruded over the surface as a pannus. The edges of nontreated defects also had characteristics of cartilaginous healing, stressing the importance of using serial sectioning techniques in this model of cartilage repair.

Stereological study of the developing distal femoral growth plate.

The distal femoral growth plate has a uniquely convoluted structure comprised of four mammillate processes. Factors contributing to the development of these processes and overall plate geometry were explored using three-dimensional image analysis of the canine distal femoral epiphysis. The growth plate at birth remains relatively flat until ossification of the epiphysis begins at 1 week of age. Epiphyseal ossification proceeds eccentrically, projecting in the medial-lateral and anterior-posterior directions. Growth plate activity indexed by [3H]thymidine labeling and plate thickness revealed regional differences in cell proliferation. This was measured as a decreased labeling index and thinning of the growth plate in areas capped by the ossifying epiphysis. The eccentric ossification pattern and associated variations in growth plate activity result in definition of an "intraphyseal" groove and medial-lateral oriented sulcus. The groove and sulcus bisect the plate into four quadrants, giving rise to a convoluted structure composed of four areas of plate elevations termed mammillary processes (MP). By 5 weeks, the pattern of ossification results in greater development of the MP in the anterior-medial quadrant and in decreasing order, in the posterior-medial, anterior, and posterior-lateral quadrants. By 10 weeks, a uniform rate of cell proliferation was observed coincident with completion of ossification of the epiphysis. The data suggest that localized variations in growth plate proliferation are associated with ossification of the epiphysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular reorganization and return of rigidity in fracture healing.

The present study addresses the relationship between vascular reorganization and the biomechanical changes occurring during canine long bone fracture healing. A middiaphyseal osteotomy of the radius was performed, and angiographic studies were carried out using India ink injections from 2 to 12 weeks postosteotomy. The radii were harvested, subjected to nondestructive four-point bend testing on an Instron, and then sectioned and cleared according to the Spaltholtz technique. The observed microangiographic patterns were correlated with the calculated rigidity values. Quantitative bone blood flow measurements around the osteotomy were performed on a different group of animals, using the radiotracer microsphere technique, at 3, 6, and 9 weeks postosteotomy to correlate with our qualitative microangiographic results. We demonstrated a direct and predictable relationship between the phase of vascular reorganization and the rigidity. This correlation was present even in our delayed union specimens.

Osteogenic growth peptide normally stimulated by blood loss and marrow ablation has local and systemic effects on fracture healing in rats.

Osteogenic growth peptide, a histone H4-related, 14-amino-acid peptide, is an active mediator of local, as well as systemic, osteogenic activity in response to marrow ablation, trauma, and blood loss. In this study, the effect of exogenous osteogenic growth peptide on the healing of femoral fractures in rats was investigated. A fracture at the midshaft of the femur was created in 50 rats. Half of the rats were injected subcutaneously with 25 ng of osteogenic growth peptide per rat per day for the first 7 days after fracture. Radiographs were taken each week, and the diameter of the callus was measured. The femurs of four animals from each group were harvested 1, 2, 3, and 4 weeks after fracture. Two femurs from each group were sectioned for histologic examination, and two were sectioned for measurement of density and mineral content. Marrow was aspirated from the contralateral femurs to establish adhering cell cultures, which were examined for osteogenicity. At 2 weeks, a large increase in mitogenicity and osteogenicity was seen in the marrow-derived cultures from the rats treated with osteogenic growth peptide; this increase was sustained through 4 weeks. Extraction of RNA from the contralateral marrow (systemic expression) and callus (local expression) for amplification with reverse transcription-polymerase chain reaction revealed greater systemic expression of transforming growth factors beta1, beta2, and beta3, fibroblast growth factor-2, insulin-like growth factor-1, and aggrecan throughout the 4 weeks after fracture, whereas types IIA and IIB collagen, link protein, and fibroblast growth factor receptor-3 had a greater local expression. The specimens treated with osteogenic growth peptide had a stronger expression of transforming growth factor-beta1, both locally and systemically. The average diameter of the callus was greater for the treated rats at all time intervals, and peak diameters were 7.58 mm at 3 weeks for the treated rats and 6.64 mm at 2 weeks and 6.63 mm at 3 weeks for the controls. Histological study revealed an earlier organization and faster healing of the treated fractures, as evidenced by the larger, earlier appearance of cartilaginous soft callus and the more rapid organization of bridging trabecular bone. No statistical significance was obtained when these comparisons were made between the groups. These results suggest that osteogenic growth peptide can be used to promote earlier proliferation and differentiation of osteogenic cells in marrow and bone-repair callus, possibly through its effect on the transforming growth factor-beta family.

Effect of aging on tensile mechanical properties of the rabbit distal femoral growth plate.

Tensile tests to failure were performed on the distal femoral growth plate of rabbits. The measured tensile forces, together with animal weight and dimensional measurements of the femur, were used to develop a noninvasive method of predicting growth failure loads and to examine the effects of age on the tensile strength of the growth plate. Growth plate failure load correlated with rabbit weight, (r = 0.93), femoral length, (r = 0.91), and contoured growth plate surface area, (r = 0.74). Regression analysis for these relationships allowed for failure load prediction if animal weight, femoral length, or growth plate surface area was known. Nominal stress (failure load/surface area) was calculated and correlated with animal weight (age) for each distal femoral growth plate utilizing two surface area estimating techniques: growth plate surface contour and growth plate cross-sectional enlargement. A strong association was found with either technique. The growth and maturation of growth plate cartilage is of major importance in pediatric orthopaedics. This study demonstrate that the age-dependent increases in tensile mechanical properties of the growth plate do not result merely from growth plate enlrgement or conformational changes. The changing tensile mechanical properties of the growth plate may explain why transphyseal distraction used clinically has produced varied and somewhat unpredictable results. Our study suggests that dose-response investigations are needed to define safe and optimal transphyseal distraction tensions before further clinical application is pursued.

Evidence for multiple routes of speech production in a case of fluent aphasia.

A case study is reported of a 24-year old woman who developed fluent aphasia with superior reading relative to auditory comprehension following herpes simplex encephalitis. Her language disturbance showed exceptional features: oral reading, repetition and naming to confrontation were severely impaired and yet her spontaneous speech recovered to be relatively intact. These features are not consistent with Wernicke's aphasia, pure word deafness or any classic aphasic syndromes. These findings indicate the presence of several routes for phonological output that may be differentially impaired.

The augmenting/reducing phenomenon in the auditory evoked potential.

Auditory evoked potentials (AEPs) were recorded to 4 intensities of tones (70, 80, 90, 100 dB) in 22 normal subjects. Augmenting (generally increasing amplitude with increasing stimulus intensity) and reducing (a levelling off or decrease in amplitude with increasing stimulus intensity) were found to occur at both central (Cz, C3, C4) and temporal (T3, T4) placements, regardless of which peak or peak-through measure was examined. There were generally low levels of agreement between central amplitude/intensity response patterns and those at temporal placements. An individual was seldom classified the same way (i.e. augmenter or reducer) when the augmenting or reducing was assessed using different AEP measures. These results suggest that in the AEP the suitability of the conventional definition and the validity of certain interpretations of augmenting/reducing are questionable.

A multiwire proportional gamma camera for imaging 99Tcm radionuclide distributions.

A gamma camera made of multiple multiwire proportional chambers with thin converter foils has been evaluated for clinical application. Results are presented from a small prototype (10 cm x 10 cm)showing good imaging of 99Tcm radionuclide distributions and comfirming the predictions of the theory regarding quantum efficiency and spatial resolution. The technique is especially aimed at creating a gamma camera with an active area greater than or approximately equal to 1 m2, a quantum efficiency of 15% and a spatial resolution approximately 3 mm, to be applied in whole body scanning and tomographic applications. The results generated by the current prototype indicate that the above requirements can be met using relatively cheap mass production techniques from the electronic industry. This apparatus is covered by patent applcation number 26595/77.

Evaluation of the Noiles hinged knee prosthesis. A five-year study of seventeen knees.

The Noiles hinged knee prosthesis has been reported to diminish sheer and tensile loading on the cement-bone interface. Theoretically, this should eliminate the complication of loosening, commonly reported in hinged total knee prostheses. We reviewed the cases of all of the patients who have been treated with the Noiles knee prosthesis at our institution. Eighteen knees in fourteen patients were available, seventeen of which were followed for more than five years. Although all of the prostheses did well initially, ten knees in eight patients (56 per cent) had failed by an average of thirty-two months postoperatively. These eight patients included four of the five who weighed more than ninety kilograms and all of those who had had a prior arthroplasty. The failures were clearly defined along the lines of sex distribution. Measurements on the radiographs showed a significant difference between sexes in the metaphyseal diameter and thus in the percentage of the femoral canal that was filled by the prosthesis and cement. We concluded that prosthetic design must incorporate cortical cement support to reduce stress at the cement-bone interface, especially in a medullary canal with a larger diameter.

Malignant hyperthermia. A potentially fatal syndrome in orthopaedic patients.

Malignant hyperthermia is an inherited muscular disorder and a cause of sudden death in afflicted patients. Stress arising from tramuma, surgery, and other causes can initiate the syndrome. We studied the types of orthopaedic problems commonly seen in patients with this condition as well as the clinical manifestations and pathophysiology of the syndrome. Recognition, management, and understanding of the pathophysiology of malignant hyperthermia can be aided by a study of its similarities to porcine stress syndrome. We performed experimental studies of muscle and prophylaxis in swine. We also demonstrated the extension of the prophylactic use of dantrolene sodium in a management protocol in eighty surgical procedures in humans.

A multicenter study of the treatment of non-union with constant direct current.

A clinical study was initiated at the University of Pennsylvania in 1970 to evaluate the use of constant direct current in treating acquired non-union. In 1977 the study was expanded to include twelve participating investigators throughout the United States. The results indicate that, given proper electrical parameters and proper cast immobilization, a rate of bone union comparable to that seen with bone-graft surgery was achieved. Experience dictated that four cathodes, each delivering twenty microamperes of constant direct current for twelve weeks, were required to heal a non-union of a long bone. Of 178 non-union in 175 patients treated with adequate electricity in the University of Pennsylvania series, 149 (83.7 per cent) achieved solid bone union. Patients with a history of osteomyelitis had a healing rate of 74.4 per cent. The presence of previously inserted metallic fixation devices did not affect the end-result healing rate. Of eighty non-unions in seventy-nine patients treated with electricity in the participating investigators' series, fifty-eight (72.5 per cent) achieved solid bone union. Review of the non-unions treated unsuccessfully with constant direct current suggested that inadequate electricity, the presence of synovial pseudarthrosis or infection, and dislodgment of the electrodes are causes for failure with the procedure. Complications of the electrical treatment were minor and there was no deep infection resulting from this procedure in patients without previous osteomyelitis. We concluded that the practicing orthopaedic surgeon utilizing constant direct current to treat non-union should, by adhering to proper fracture management and by following the biophysical principles described herein, be able to achieve a rate of union comparable to that of bone-graft surgery, with a lower associated risk.

The biomechanical behavior of healing canine radii and ribs.

An experimental study and accompanying theoretical study of the biomechanics of healing canine ribs and radii have been conducted. Biomechanical behavior of the healing bones was determined experimentally by whole bone structural tests in four point bending. The experimental results indicated that the non-weight-bearing ribs regained bending stiffness more rapidly than bending stiffness, while the weight-bearing radii regained bending stiffness more rapidly than bending strength. These differences were not found to correlate with differences in overall callus biochemistry, but physical examinations of the bone suggested that differences in callus morphological details between the two bone types might offer an explanation. Utilizing a theoretical model, a parameter study of the influence of callus geometry and morphology on bending behavior was conducted. The results of the parameter study demonstrate that the experimentally observed variations in the amount and distribution of callus materials and in bone geometry can produce the qualitative biomechanical differences measured experimentally. The results of the parameter study also demonstrate that bending stiffness must be used with caution as a healing criterion since it does not necessarily reflect structural strength.