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Hypothesis for the influence of fixatives on the chromatin patterns of interphase nuclei, based on shrinkage and retraction of nuclear and perinuclear structures.

Nuclear chromatin patterns are used to distinguish normal and abnormal cells in histopathology and cytopathology. However, many chromatin pattern features are affected by aspects of tissue processing, especially fixation. Major effects of aldehyde and/or ethanol fixation on nuclei in the living state include shrinkage, chromatin aggregation and production of a 'chromatinic rim'. The mechanisms of these effects are poorly understood. In the past, possible mechanisms of fixation-induced morphological change have been considered only in terms of the theoretical model of the nucleus, which involves only a random tangle of partly unfolded chromosomes contained within the nuclear membrane. Such a model provides no basis for chromatin to be associated with the nuclear envelope, and hence no obvious clue to a mechanism for the formation of the 'chromatinic rim' in fixed nuclei. In recent years, two new models of nuclear structure have been described. The nuclear membrane-bound, chromosomal-domain model is based on the discoveries of chromatin-nuclear membrane attachments and of the localisation of the chromatin of each chromosome within discrete, exclusive parts of the nucleus (the 'domain' of each partly unfolded chromosome). The nuclear matrix/scaffold model is based on the discovery of relatively insoluble proteins in nuclei, which it suggests forms a 'matrix' and modulates gene expression by affecting transcription of DNA. Here, a hypothesis for fixation-associated chromatin pattern formation based mainly on the first model but partially relying on the second, is presented. The hypothesis offers explanations of the variations of appearance of nuclei according to fixation (especially air-drying versus wet-fixation with formaldehyde, glutaraldehyde or ethanol); the appearances of the nuclei of more metabolically active versus less metabolically active cells of the same type; the appearances of nuclei after fixation with osmium tetroxide; and of the marked central clearing ('egg-shell' or 'orphan Annie' appearance) of tumour nuclei of papillary carcinoma of the thyroid gland. A similar process may underlie the phenomenon of 'chromatin margination' seen in apoptosis. Various tests of the hypothesis, such as time-lapse confocal microscopy of living nuclei during fixation, are suggested. The significance of the theory is that it suggests that chromatin patterns could be investigated in terms of qualitative and quantitative aspects of nuclear components, and hence be related to the results of studies of the structure and function of nuclei in health and disease.

Cell Nucleus↗

Comparison of dynamic versus static external fixation for pediatric femur fractures.

External fixation of pediatric femoral shaft fractures has the advantages of minimal dissection and early weight bearing. However, it is associated with slow healing and potential for refracture. Some surgeons have proposed that axial dynamization may improve the speed and strength of callus formation. to test this hypothesis, we performed a randomized controlled trial using 53 femur fractures in 52 patients between 1995 and 1999. Patients were randomized to receive dynamic or static fixation. Average time until early callus formation was 23.2 days for dynamic fixation and 24.9 days for static fixation (P = 0.627). Average time until complete radiographic healing was 70.1 days for dynamic fixation and 63.1 days for static fixation (P = 0.370). Similarly, the differences in time to fixator removal and to full weight bearing did not reach statistical significance. The conclusion was that axial dynamization of external fixation for pediatric femur fractures has no significant effect on time to healing or frequency of complications.

Child↗

Management of tibial fractures with Orthofix axial external skeletal fixator in 15 dogs.

In the present study, the applicability of fixator, surgical time, time to weightbearing, the healing time and complications of tibial fractures in dogs after fixation with Orthofix axial external skeletal fixator were evaluated. The study was performed on 15 cases which were presented to the Clinics of Small Animal Surgery. After the determination of the fracture type, fracture location, appropriate screw diameter and the location of the first screw on the fragment according to preoperative radiographs, the dogs were placed under general anaesthesia and the fixator was applied with cranio-medial approach to the tibia. Clinical and radiological examinations were continued until the removal of the external skeletal fixators at three different times (at approx. days 45, 60 and 75) according to the clinical and radiological fracture healing. The treatment results were determined by the Modified Hannover Veterinary Medicine Faculty Small Animal Fracture Evaluation Scale. The results were excellent in eight cases (53.3%), good in four cases (26.7%), fair in one case (6.7%) and poor in two cases (13.3%). Based on this study, the use of external skeletal fixation with Orthofix axial external skeletal fixator can be recommended for dogs with tibial fractures as long as careful pin tract management is performed. Further investigation is needed to determine the use of Orthofix axial external skeletal fixator for the management of other long bone fractures.

Animals↗

Mechanical evaluation of transosseous wire rope configurations in a large animal external fixator.

By use of wire ropes as the transosseous component, an external skeletal fixator for the repair of long bone fractures in horses and cattle has been designed and tested in axial compression. Theoretical methods were used in the design process to size fixator components; however, our results suggest that conventional methods of analyzing the displacement of the transosseous component may not apply to wire ropes. Large pretensions in the wire ropes are necessary to obtain functional stiffnesses for fracture fixation. Therefore, a method was sought for terminating the ropes so that an appropriate pretension could be introduced into the rope through its interface with the fixator rings. Ropes were terminated by use of 5 methods and were tested in axial tension to failure. These methods included 3 copper sleeve arrangements, welded ends, and drum sockets. The drum sockets (57.6% of rope breaking strength) far exceeded the strengths provided by the copper sleeves (8.5 to 26.6%) and the welded ends (44.3%). Using the drum sockets, 5 rope configurations were assembled to the fixator, using wood blocks to simulate bones with a gap defect. The fixator was loaded in axial compression for each of the rope configurations, and stiffnesses were determined from measured axial displacement and applied load. The 4-ring fixator configuration, with 2 ropes at 60 degrees angular separation/ring, was the stiffest. In a worst case (gap) model, a mean axial compression load of 1,730 N was observed at 2 mm of displacement for a 4-ring fixator configuration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of formalin, ethanol, and Histochoice fixation on the PCR amplification from paraffin-embedded breast cancer tissue.

The polymerase chain reaction (PCR) has been successfully employed for the laboratory analyses of genetic and infectious disorders using DNA extracted from paraffin-embedded tissues. However, fixative type and fixation time influenced PCR reactions and in some circumstances amplification fragments could not be efficiently generated. In this study, we determined the effects of three commonly used fixatives including ethanol, formalin and Histochoice, on the PCR amplification of DNA from paraffin-embedded breast cancer tissue. The effect of fixatives and fixation times was measured by the ability of the extracted DNA to serve as a template for the amplification of 280 and 530 base pair DNA fragments. On amplifying DNA, positive reactions were uniformly seen in the ethanol specimens. The next best fixative was Histochoice with positive results almost constantly observed in the PCR reactions performed. Formalin fixation sometimes compromised DNA amplification. Our results are consistent with previous reports investigating the effect of ethanol and formalin fixation on DNA amplification by PCR. Moreover, this is the first study showing that paraffin-embedded tissues fixed with Histochoice can be efficiently used for PCR gene amplification.

Breast Neoplasms↗

Iliosacral screw fixation: early complications of the percutaneous technique.

OBJECTIVE: To report on the early complications related to the percutaneous placement of iliosacral screws for the operative treatment of displaced posterior pelvic ring disruptions. STUDY DESIGN: Prospective, consecutive. SETTING: Level-one trauma center. PATIENTS: One hundred seventy-seven consecutive patients with unstable pelvic ring fractures. One hundred two male and seventy-five female patients ranging in age from eleven to seventy-eight years (mean, thirty-two years). INTERVENTIONS: Operative procedures were performed urgently according to the patient's clinical condition. Anterior pelvic reductions and fixations were performed by using internal and external fixation techniques. Accurate closed or open reductions of the posterior pelvic ring disruptions were accomplished by using a variety of surgical techniques dependent on the specific pattern of pelvic ring disruption. Closed manipulative reductions of the posterior pelvic ring were attempted for all patients. Open reductions were necessary in those patients with unacceptable closed manipulative reductions as assessed fluoroscopically at the time of operation (more than one centimeter in any field of fluoroscopic imaging). MAIN OUTCOME MEASURES: Plain inlet and outlet radiographs were obtained postoperatively at six weeks, three months, and twelve months. A pelvic computed tomography scan was performed postoperatively to assess fracture or dislocation reduction and the implant safety. Annual follow-up pelvic radiographs were obtained. Residual pelvic deformities were quantified based on these imaging modalities. RESULTS: There were no posterior pelvic infections. Minimal blood loss was associated with this technique. Complications occurred due to inadequate imaging, surgeon error, and fixation failure. Fluoroscopic imaging was inadequate due to obesity or abdominal contrast in eighteen patients. Five screws were misplaced due to surgeon error. One misplaced screw produced a transient L5 neuropraxia. Fixation failures related to either crandiocerebral trauma, delayed union, noncomplicance, and a deep anterior pelvic polymicrobial infection secondary to a urethral tear occurred in seven patients. There were two sacral nonunions that required debridement, bone grafting, and repeat fixation prior to healing. CONCLUSIONS: Iliosacral screw fixation of the posterior pelvis is difficult. The surgeon must understand the variability of sacral anatomy. Quality triplanar fluoroscopic imaging of the accurately reduced posterior pelvic ring should allow for safe iliosacral screw insertions. Anticipated noncompliant patients or those with craniocerebral trauma may need supplementary posterior pelvic fixation. Low rates of infection, blood loss, and nonunion can be expected.

Adolescent↗

Traditional methods vs rigid internal fixation of mandible fractures.

OBJECTIVE: To compare traditional methods (ie, intermaxillary fixation with interosseous wiring or external fixation) with newer techniques (ie, plating, use of lag screws) of open reduction and fixation of mandible fractures. DESIGN: Retrospective analysis of data from medical records. SETTING: Academic urban medical center. PATIENTS: Nonrandomized sample of 356 patients admitted to the hospital for treatment of mandible fractures from 1987 through 1991; 155 patients treated with open reduction and fixation were studied. INTERVENTIONS: Sixty-nine patients were treated with interosseous wire fixation or external fixation, 86 patients with rigid internal fixation. MAIN OUTCOME MEASURES: Presence of infection, nerve impairment, nonunion, malunion, operative time, and follow-up. RESULTS: No significant difference was noted between the two groups for sex, treating service, delay in presentation, antibiotic coverage, mechanism of injury, or type of fracture. The incidence of infection, nerve injury, and unavailability for follow-up were greater in patients treated by the newer techniques. Overall expense and operative time were greater in the group treated with plates and lag screws. CONCLUSIONS: We advocate traditional techniques for patients with mandible fractures requiring open reduction and fixation.

Bone Plates↗

Superior preservation of the staphylococcal glycocalyx with aldehyde-ruthenium red and select lysine salts using extended fixation times.

The utility of lysine-based aldehyde-ruthenium red fixatives for the preservation and/or staining of the fibrous staphylococcal glycocalyx was improved by substitution of alternative forms of lysine for the free amino form. Paraformaldehyde-glutaraldehyde fixatives containing alternative lysines, with or without ruthenium red, were compared at short 20-minute prefixation times and at extended overnight fixation times. Although inclusion of paraformaldehyde made longer fixation times possible, the length of time for "safe" fixation varied per sample and could not be predicted. All alternative lysine forms permitted fixation of at least 24 hours without sample loss. The L-lysine monohydrochloride or L-lysine acetate forms permitted longer fixation times than the L-lysine free amino form, and they had comparable or better preservation of the staphylococcal glycocalyx. Thus, the usefulness of aldehyde-lysine-based fixatives with minor changes has been enhanced.

Aldehydes↗

Immunostaining of cell preparations: a comparative evaluation of common fixatives and protocols.

Immunostaining of cytologic preparations has been beset by problems of inconsistency, high background staining, and the requirement of different fixatives for different antigens. This study sought to identify a universal fixative and a simple fixation protocol suitable for a wide range of tissue antigens commonly employed for cytologic diagnosis. In an analysis of 23 fixation protocols involving acetone, acetone/methanol, acetone/formalin, glutaraldehyde, ethanol, methanol, and formal saline, fixation in 0.1% formal saline overnight at 27 degrees C followed by 10 min fixation in 100% ethanol produced the most consistent and optimal preservation of immunoreactivity which could be further enhanced by pre-treatment with microwaves for epitope retrieval. Blocking of endogenous peroxidase was not necessary with this fixation protocol. Provided the smears were well air-dried (for at least 14 hr) prior to immersion in formal saline, there was no need to employ adhesive-coated glass slides. The smears could be kept at 27 degrees C (room temperature) for at least 7 days and at -70 degrees C for 5 wk without loss of immunoreactivity as air-dried smears or after fixation in formal saline. One hundred percent acetone and 100% ethanol produced good morphology and immunoreactivity but a high level of background staining, whereas acetone-based mixtures resulted in inconsistent immunostaining.

Acetone↗

Fixation of mammalian cells for flow cytometric evaluation of DNA content and nuclear immunofluorescence.

Mammalian tissue culture cells were fixed with 3 different alcoholic fixatives--acetone:methanol, EtOH, and MeOH. The quality of the resulting DNA histograms was evaluated by comparison of CV, G1/G2 ratio, G1 mode, cell aggregation, and debris formation; 81-90% MeOH (final concentration) was determined to be the optimal fixative by these criteria. A procedure was then examined using a prefix with paraformaldehyde followed by MeOH (PF/MeOH). This procedure produced cell preparations with reduced debris and aggregation, equivalent mode and ratio, but increased CV when compared with MeOH fixation. Both MeOH and PF/MeOH fixation procedures were then compared for their utility in dual staining for DNA and intracellular immunofluorescence for a nuclear protein, SV40 T antigen (Tag). Since alcohols are known to affect immunofluorescence staining of some antigens, fixation with paraformaldehyde followed by Triton X-100 permeabilization (PF/TX) was also included in this comparison to generalize the study by providing an alternative to MeOH permeabilization. The three procedures were evaluated for the quality of the sample by measuring the same descriptors of the DNA parameter as in the alcohol study. PF/TX consistently produced samples with decreased DNA CV and less debris and aggregation compared to MeOH methods. Two criteria were used to evaluate immunofluorescence--the amount of Tag measured and reproducibility. All MeOH methods were equivalently reproducible with CV's less than 3%. PF/TX was slightly less so with a CV of less than 6%. In contrast, different levels of Tag were measured for each procedure. For mouse 3T3 cells infected with a recombinant retroviral vector encoding T antigen, the level of T antigen measured after PF/MeOH was 21% greater than in MeOH fixed cells, and the level in PF/TX fixed cells was 37% less. The fraction of fluorescence specific to T antigen for these cells was 79-83% for all procedures. The lower levels measured after fixation by PF/TX were shown to be due to epitope masking. Why higher levels are measured with PF/MeOH procedures is unknown at present but may be due to antigen retention. Therefore, each of these fixation methods may be used with confidence in reliability but they are not equivalent with respect to the molecular architecture of the nucleus. It is postulated that PF/TX permeabilizes cells but cells retain native supramolecular structure, whereas MeOH based fixatives disrupt this structure and randomize availability of epitope to antibody. If so, the two procedures could be used as complementary procedures to study gene expression and function.

Acetone↗

Sequential paraformaldehyde and methanol fixation for simultaneous flow cytometric analysis of DNA, cell surface proteins, and intracellular proteins.

A cell fixation and permeabilization procedure consisting of sequential paraformaldehyde and methanol was evaluated and found suitable for concomitant flow cytometric quantification of total cellular DNA, immunofluorescence measurements of cell surface proteins, and immunofluorescence measurements of intracellular proteins. Paraformaldehyde/methanol-fixed cells exhibited significantly greater intracellular antitubulin immunofluorescence than cells fixed with paraformaldehyde or methanol alone (p less than 0.002) and significantly greater intracellular antitubulin immunofluorescence than cells fixed with methanol followed by paraformaldehyde (p less than 0.006). With paraformaldehyde/methanol fixation, cell morphology was well preserved and forward and right angle light scatter properties were sufficiently well maintained to permit gating on these parameters. Cell surface marker staining with fluorescent anti-leukocyte antibodies was unaffected by fixation with paraformaldehyde/methanol. Paraformaldehyde effects on the intensity of DNA staining with propidium iodide were dependent on paraformaldehyde concentration and fixation temperature; these effects were least pronounced at low paraformaldehyde concentrations (0.25% or less), and at temperatures lower than 37 degrees C. Paraformaldehyde fixation may result in differences in propidium iodide staining of DNA in some diploid cells, which may produce small spurious aneuploid peaks in normal peripheral blood leukocytes. Paraformaldehyde fixation also produces an apparent increase in the DNA index of aneuploid cell populations in comparison with methanol fixation, particularly when the DNA index exceeds 1.5. Occasionally, this paraformaldehyde fixation-induced effect is useful in identifying biologically distinct near-diploid subpopulations in tumors.

Aneuploidy↗

Closed reduction and percutaneous fixation of anterior column acetabular fractures.

OBJECTIVE: The current standard treatment of anterior column acetabular fractures includes formal open reduction with internal fixation (ORIF) through a variety of anterior approaches. These approaches have been associated with significant blood loss, infection, lengthy operative times, and neurovascular complications. It therefore seems reasonable to consider less invasive alternatives to conventional treatment methods. A technique for percutaneous reduction and fixation of a particular acetabular fracture pattern is presented. Execution of this technique has been facilitated by the use of image-guided surgical navigation. MATERIALS AND METHODS: A retrospective review was performed on 23 patients who had suffered an acute anterior column fracture of the acetabulum (OTA 62-A3.2, 62-A3.3, 62-B3.2, 62-B3.3) managed with closed reduction and internal fixation using large-bore cannulated screws over an 11-year period. An additional three patients treated during the study period underwent formal ORIF with plates and screws after failure of attempted closed reduction, and were not included in this analysis. Eight of the 23 patients had an associated posterior hemitransverse fracture that was also managed with minimally invasive fixation. A variety of surgical navigation techniques were used to allow accurate percutaneous screw placement: CT-guided percutaneous fixation was performed in 10 patients (1990-1995); fluoroscopy alone was used in four patients (1995-1998); and computer-assisted virtual fluoroscopy was used in nine patients (1999-2002). Some fractures were nondisplaced but potentially unstable, and involved the superior weight-bearing dome; others required closed manipulation using Schanz-pin joysticks placed into the iliac wings and held in place with a temporary external fixator. One patient required a limited open reduction followed by percutaneous screw fixation. After confirmation of adequate reduction, one to three large-bore cannulated screws were placed percutaneously using previously defined safe trajectories. All patients were managed postoperatively with early mobilization and physical therapy. RESULTS: The average preoperative and postoperative displacements were 8.9 and 2.4 mm, respectively. No patient had a loss of reduction during healing. As experience was gained with the computer-assisted imaging, total fluoroscopy times were as little as 6 s, and were routinely kept below 45 s. None of the patients experienced infection, significant blood loss, or iatrogenic neurologic or visceral injury. No symptomatic heterotopic ossification was noted. Of those patients available for follow-up at a minimum of 2 years, the average HSS self-administered hip score was 91. CONCLUSION: We believe that our findings substantiate percutaneous reduction and internal fixation of anterior column acetabular fractures as a safe and effective alternative to formal ORIF, with a low anticipated complication rate and excellent outcome.

Acetabulum↗

The bovine pericardial xenograft: II. Effect of tethering or pressurization during fixation on the tensile viscoelastic properties of bovine pericardium.

Our previous article suggested that control of the extensibility of aldehyde-fixed pericardium could be achieved by controlling shrinkage during fixation. Therefore, to prevent shrinkage, we have used sandpaper-lined plexiglass plates to clamp circular samples of bovine pericardium during fixation in glutaraldehyde, tethering them at their original dimensions. As well, we have applied transmural pressures of 50 or 100 mm Hg during fixation using a hydraulic column of glutaraldehyde solution. Strips cut at 0 degree, 30 degrees, 60 degrees, and 90 degrees to the base-to-apex cardiac direction have been examined for cyclic stress-strain response, stress relaxation, plastic deformation, and fracture behavior. Under physiological stresses, tethered and pressure-fixed materials were both nearly isotropic. Tethering during fixation produced a material with extensibility nearly identical to that of fresh tissue. Plastic deformation during cyclic loading was reduced below that seen in simple fixation while stress relaxation was unchanged. Pressure-fixation produced reduced extensibility similar to that produced in porcine aortic valve leaflets. Plastic deformation and stress relaxation were both markedly reduced. Pressure-fixation reduced the strain at fracture, but fracture behavior was otherwise unaffected. Tethering and pressure-fixation offer attractive means to control the mechanical behavior of bovine xenograft materials.

Animals↗

The bovine pericardial xenograft: III. Effect of uniaxial and sequential biaxial stress during fixation on the tensile viscoelastic properties of bovine pericardium.

Our previous two articles have shown that glutaraldehyde-fixed bovine pericardium is nearly isotropic, whether fixed without constraints, with tethering, or with pressure. In this study, we have used uniaxial stress during fixation to produce bovine pericardial material with marked tensile anisotropy. Rectangular and cruciate pericardial samples have been mechanically examined after one of four treatments: (i) fixation under 88-kPa uniaxial stress, (ii) fixation under 176-kPa uniaxial stress, (iii) 3 h of 176-kPa uniaxial stress in saline followed by 24-h fixation under the same stress, (iv) fixation under 176-kPa uniaxial stress followed by a second fixation under 176-kPa stress in a direction normal to the first. Strips of material were cut at 0 degree, 30 degrees, 60 degrees, and 90 degrees to direction of the initial stress, and tested for response to cyclic loading, stress relaxation, plastic deformation, and fracture properties. Fixation under uniaxial stress produced anistropy similar to that seen in porcine aortic valve leaflets; however, the overall extensibility of the material depended on the applied stress and the aspect ratio of the stressed sample. While loading in saline produced no change, the sequential biaxial stressing produced a reduction in anisotropy, suggesting exposure of additional crosslinking sites. Uniaxial stress during fixation may be a useful method for construction of anisotropic heart valve leaflets.

Animals↗

Effect of fixation-resin combinations and ruthenium red on elucidating outer envelope structure and surface morphology of two methanotrophic bacteria.

We examined the ultrastructure of the cell envelope in Type I, Methylomonas albus (BG8), and Type II, Methylosinus trichosporium (OB3b), methane-oxidizing bacteria by using different fixatives, ruthenium red (RR) combinations and resins. We compared LR White and Spurr embedments with the following fixations: glutaraldehyde/OsO4, two glutaraldehyde-paraformaldehyde, and two different en bloc ruthenium red procedures, one utilizing OsO4 and the other with glutaraldehyde/OsO4 in sequential fixation. These fixations were also studied by scanning electron microscopy (SEM). Unfixed cells prepared by freeze etch were used for comparison. Transmission electron microscopy of BG8 embedded in LR White resin (with or without red0 preserved a layer of cup-like structures that were not seen in Spurr resin-embedded cells unless ruthenium red was used. For OB3b, the second RR method preserved beads and filaments where only "spike-like" structures were seen in all other fixations in both resins. By SEM, all fixations preserved a capsular slime layer of BG8 that was removed from some cells by both RR methods. In all SEM fixations, a bead layer was preserved in OB3b that was enhanced by RR. Filaments seen by freeze-etch and thin-section techniques were not seen in SEM. Presence or absence of particular envelope structures in these methanotrophs is dependent on the combination of fixatives and/or resins employed and is species-specific. The chemical preparation methods used resulted in enhanced understanding of the structure and composition of the cell envelope.

Cell Membrane↗

The effect of a series of fixatives on the AgNOR technique.

With increasing interest being shown in nucleolar organizer regions (NORs) in pathology, it was considered of great importance to evaluate the effect of some of the more commonly used and more specialized fixatives on the demonstration of these moieties. NORs can be demonstrated in paraffin sections by a silver technique (AgNOR method) which was developed from a method used by cytogeneticists for the demonstration of NORs in chromosome spreads. The degree of staining is dependent on the fixation regime employed and results may vary greatly from one fixative to another. The fixative schedules and post-treatments used in this study were based on standard sequences from the literature. We have shown that, in general, alcohol-based fixatives give optimal results, Carnoy's fluid being especially recommended. Mercurial and dichromate-containing fixatives were found to have highly detrimental effects on NOR staining. 'Routine' 10 per cent formol saline fixation gave adequate results whereas 10 per cent neutral buffered formalin gave optimal staining, similar to alcohol-based fixation.

Fixatives↗

The dorsomedial frontal cortex of the macaca monkey: fixation and saccade-related activity.

The activity of 249 neurons in the dorsomedial frontal cortex was studied in two macaque monkeys. The animals were trained to release a bar when a visual stimulus changed color in order to receive reward. An acoustic cue signaled the start of a series of trials to the animal, which was then free to begin each trial at will. The monkeys tended to fixate the visual stimuli and to make saccades when the stimuli moved. The monkeys were neither rewarded for making proper eye movements nor punished for making extraneous ones. We found neurons whose discharge was related to various movements including those of the eye, neck, and arm. In this report, we describe the properties of neurons that showed activity related to visual fixation and saccadic eye movement. Fixation neurons discharged during active fixation with the eye in a given position in the orbit, but did not discharge when the eye occupied the same orbital positions during nonactive fixation. These neurons showed neither a classic nor a complex visual receptive field, nor a foveal receptive visual field. Electrical stimulation at the site of the fixation neurons often drove the eye to the orbital position associated with maximal activity of the cell. Several different kinds of neurons were found to discharge before saccades: 1) checking-saccade neurons, which discharged when the monkeys made self-generated saccades to extinguish LED's; 2) novelty-detection saccade neurons, which discharged before the first saccade made to a new visual target but whose activity waned with successive presentations of the same target. These results suggest that the dorsomedial frontal cortex is involved in attentive fixation. We hypothesize that the fixation neurons may be involved in codifying the saccade toward a target. We propose that their involvement in arm-eye-head motor-planning rests primarily in targeting the goal of the movement. The fact that saccade-related neurons discharge when the saccades are self initiated, implies that this area of the cortex may share the control of voluntary saccades with the frontal eye fields and that the activation is involved in intentional motor processes.

Animals↗

Behavioral modulation of neuronal activity in monkey striate cortex: excitation in the absence of active central fixation.

Two rhesus monkeys were trained to fixate a small fixation point for randomly varying periods of time using the dimming paradigm. During single unit recording in the striate cortex the fixation point was turned off for a few hundred milliseconds in the presence of a peripheral stimulus. During the disappearance of the fixation point the peripheral stimulus could dim and because of that, in some trials the monkey's saccade to the stimulus right after the offset of the fixation point. In other trials of the same task the monkeys suppressed the execution of a saccade without missing the dimming of the stimulus. During the monkeys performance of this task, striate cortex neurons display an increase of activity after fixation point offset in the presence of a receptive field stimulus, independent of the monkey's decision to look at it or not. Its occurrence can be interpreted as a sign of the monkey having interrupted active fixation of the fixation point and/or having shifted its visual attention towards the peripheral target without necessarily executing a saccade to it.

Animals↗