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Biomedical subjects

J S Berger

Publications and source records attributed to J S Berger.

12 recordsLinked to original sources

Behavioral and neurophysiological correlates of episodic coding, proactive interference, and list length effects in a running span verbal working memory task.

Updating refers to (1) discarding items from, (2) repositioning items in, and (3) adding items to a running working memory span. Our behavioral and fMRI experiments varied three factors: trial length, proactive interference (PI), and group integrity. Group integrity reflected whether the grouping of items at the encoding stage was violated at discarding. Behavioral results were consistent with the idea that updating processes have a relatively short refractory period and may not fatigue, and they revealed that episodic information about group context is encoded automatically in working memory stimulus representations. The fMRI results did not show evidence that updating requirements in a task recruit executive control processes other than those supporting performance on nonupdating trials. They did reveal an item-accumulation effect, in which signal increased monotonically with the number of items presented during the trial, despite the insensitivity of behavioral measures to this factor. Behavioral and fMRI correlates of PI extended previous results and rejected an alternative explanation of PI effects in working memory.

Adult↗

Activity in human frontal cortex associated with spatial working memory and saccadic behavior.

We examined, with event-related fMRI, two hypotheses about the organization of human working memory function in frontal cortex: (1) that a region immediately anterior to the frontal eye fields (FEF) (superior frontal cortex, SFC) is specialized for spatial working memory (Courtney, et al., 1998); and (2) that dorsolateral prefrontal cortex (PFC) plays a privileged role in the manipulation of spatial stimuli held in working memory (Owen, et al., 1996; Petrides 1994). Our delayed-response task featured 2-D arrays of irregularly arranged squares that were highlighted serially in a random sequence. The Forward Memory condition required maintenance of the spatio-temporal sequence, the Manipulate Memory condition required reordering this sequence into a new spatially defined order, the Guided Saccade condition required saccades to highlighted squares in the array, but no memory, and the Free Saccade condition required self-paced, horizontal saccades. The comparison of fMRI signal intensity associated with 2-D saccade generation (Guided Saccades) versus fMRI signal intensity associated with the delay period of the working memorials condition revealed no evidence for greater working memory-related activity than saccade-related activity in SFC in any individual subject, nor at the level of the group, and greater 2-D saccade than delay-period activity in three of five subjects. These results fail to support the hypothesis that spatial working memory-related activity is represented preferentially in a region of SFC anterior to the FEF (Courtney, et al., 1998). The comparison of maintenance versus manipulation of spatio-temporal information in working memory revealed significantly greater activity associated with the latter in dorsolateral PFC, but not in ventrolateral PFC or in SFC. These results suggest that the delay-related function of SFC is limited to the maintenance of spatial information, and that this region does not support the nonmnemonic executive control functions supported by dorsolateral PFC. These results also indicate that the preferential recruitment of dorsolateral PFC for the manipulation of information held in working memory applies to tasks employing spatial stimuli, as well as to tasks employing verbal stimuli (D'Esposito, et al., 1999); Petrides et al., 1993; Postle et al., 1999).

Acoustic Stimulation↗

Functional neuroanatomical double dissociation of mnemonic and executive control processes contributing to working memory performance.

We used event-related functional MRI to investigate the neural bases of two categories of mental processes believed to contribute to performance of an alphabetization working memory task: memory storage and memory manipulation. Our delayed-response tasks required memory for the identity and position-in-the-display of items in two- or five-letter memory sets (to identify load-sensitive regions) or memory for the identity and relative position-in-the-alphabet of items in five-letter memory sets (to identify manipulation-sensitive regions). Results revealed voxels in the left perisylvian cortex of five of five subjects showing load sensitivity (as contrasted with alphabetization-sensitive voxels in this region in only one subject) and voxels of dorsolateral prefrontal cortex in all subjects showing alphabetization sensitivity (as contrasted with load-sensitive voxels in this region in two subjects). This double dissociation was reliable at the group level. These data are consistent with the hypothesis that the nonmnemonic executive control processes that can contribute to working memory function are primarily prefrontal cortex-mediated whereas mnemonic processes necessary for working memory storage are primarily posteriorly mediated. More broadly, they support the view that working memory is a faculty that arises from the coordinated interaction of computationally and neuroanatomically dissociable processes.

Cerebral Cortex↗

Antibodies to chondroitin sulfate C: a new detection assay and correlations with neurological diseases.

Antibodies to chondroitin sulfate C (ChS C) have been previously associated with sensory axonal neuropathy. Investigation of these antibodies has, however, been limited by the lack of a sensitive and reliable test for their detection. We developed a new enzyme-linked immunoassorbent assay (ELISA), where biotinylated ChS C was made to adhere to avidin-coated microwells. The new ELISA showed a much greater sensitivity than other currently available ELISAs for detection of anti-ChS C antibodies. A total of 480 sera (466 patients and 14 normal volunteers) were tested at increasing dilutions for anti-ChS C antibody activity. Normal subjects had IgM anti-ChS C antibody titers of up to 3,200 and mildly elevated titers of 6,400 were seen in a variety of diseases. Eleven patients had titers of 12,800 or higher. These included seven patients with sensory axonal neuropathy, three with amyotrophic lateral sclerosis and one with corticobasal ganglionic degeneration. These studies indicate that anti-ChS antibodies do occur in patients with axonal sensory neuropathy, but are not limited to that disease.

Antibodies, Monoclonal↗

Stabilization of helical peptides by mixed spaced salt bridges.

Whether or not surface salt bridges have a strong stabilizing effect on the native structure in proteins remains uncertain. Previous studies of model peptides have shown that salt bridges spaced at i,i +4 along the chain are more stabilizing than those spaced at i,i +3, with a preference for the order acid-base rather than base-acid from N to C terminus. An analysis of the effect of spacing the ion pairs in short helical peptides is presented, in which acidic and basic side chains spaced two or three residues apart alternate along the chain. The mixed spacing proves to be stabilizing relative to pure spacings. A control peptide in which salt bridges were spaced uniformly three residues apart proved to form a beta-sheet structure rather than alpha-helix. This is due to formation of a silk-like apolar face consisting of alanine side chains; the mesoscopic structure formed by these sheets can be imaged by scanning microscopy.

Alanine↗

The mandibular repositioning device: role in the treatment of obstructive sleep apnea.

The role of oral appliances in the routine treatment of obstructive sleep apnea (OSA) is not well defined. This prospective study attempts to clarify the clinical role of a specific oral appliance, the mandibular repositioning device (MRD). This study evaluated the demographic, polysomnographic, and cephalometric radiographic findings predictive of treatment success or failure with the MRD. Twenty-nine patients were diagnosed with mild to severe OSA by nocturnal polysomnography. The majority of these patients were intolerant to nasal continuous positive airway pressure (CPAP) and all were fitted with a MRD. Twenty-three of these patients were compliant initially with MRD use and received post-treatment nocturnal polysomnogrpahy at a mean of 104 days after receiving the device. The respiratory disturbance index (RDI) decreased with MRD use (37 +/- 23 versus 18 +/- 20 events/hour, p < 0.001), and 16 of the 23 patients (69%) were considered responders (decrease in RDI > or = 50% and posttreatment RDI < or = 20). Measurements of subjective and objective daytime sleepiness, nocturnal oxygen desaturation, and snoring were all improved with MRD use. A pre-treatment RDI > 40 was present in four of the seven (67%) non-responders. Age, body mass index, and cephalometric radiographic measurements were not predictive of treatment outcome. Sixteen of 23 patients (70%) continue to use the MRD after 3.4 +/- 0.7 years. This study suggests that the MRD is useful in the long-term treatment of patients with OSA of mild to moderate severity.

Adult↗

Poly(adenosine diphosphoribose) polymerase in peripheral blood leukocytes from normal donors and patients with malignancies.

A two-color flow cytometric technique was developed to analyze poly(ADP-ribose) polymerase (PADPRP) in different individuals as a function of different physiological or pathological conditions and to establish the basis for determining whether enzyme deficiency may predispose to degenerative or malignant disorders. Peripheral blood granulocytes were devoid of enzyme activity, whereas mononuclear cells had variable amounts. PADPRP was highest in B cells, intermediate in T cells, and lowest in monocytes. This pattern of enzyme distribution and relative enzyme content of different types of cells was remarkably constant in normal subjects. In a series of 66 normal donors there was no significant biological variation in enzyme content as a function of age, race, or sex. The mean PADPRP values in peripheral blood mononuclear cells from 81 random patient samples obtained from an ambulatory oncology clinic did not differ significantly from normal subjects. However, groups of patients with breast cancer, lymphocytic malignancies, and esophageal cancer were observed to have below normal levels for peripheral blood mononuclear cell PADPRP.

Adult↗

Cyclosporine induces abnormal facial bone growth in children: a preliminary study.

Using cephalometric radiography, facial bony structure of a group of pediatric renal transplant recipients immunosuppressed with cyclosporine (CsA) and prednisone was studied and compared with a control group of children. A pattern of abnormal facial growth was demonstrated on cephalometry in eight of nine transplant recipients receiving CsA. The abnormalities included shortening of posterior facial height and increased anterior facial height with a deep mandibular plane angle. There was also an absolute shortening in the mandibular body and mandibular retrognathia. These findings may be consistent with inhibition of mandibular condylar growth inhibiting the anteroinferior growth of the mandible. Similar changes were present in two children with end-stage renal disease and none of the remaining nine control patients (P less than 0.01, chi-squared analysis). The affected area appears to be the lower third of the face. The role of CsA in affecting facial bony growth in children needs to be evaluated further.

Adolescent↗

Alveolar atrophy and decreased skeletal mass of the radius.

Using absorptiometry, the bone calcium mass (BCM) at two different sites of the radius was measured in 12 male patients referred for vestibuloplasty of the mandible. The most distal site contained both cortical and cancellous bone while the other site contained cortical bone only. The BCM values were compared with those for normal patients of the same age. The patients with mandibular atrophy all had less bone in the radius than their age-matched controls (p less than 0.01). This is indicative of a systemic factor or factors operating both in the mandible and in the radius. The examination prior to oral surgery should therefore include an evaluation for diseases causing general bone loss.

Absorption↗

Interpositional bone graft augmentation of the atrophic mandible: a preliminary report.

The mandible is sectioned in an oblique direction and an iliac crest graft is placed between the fragments for augmentation of an atrophied mandible. The technique was used in 12 patients; follow-up examinations included serial panoramic radiographs and recording of changes in mandibular height. A 10% to 27% loss of the height gained occurred between three and 12 months postoperatively.

Adult↗