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Biomedical subjects

Peter M Black

Publications and source records attributed to Peter M Black.

At least 19 recordsLinked to original sources
PubMed2007

Aberrant splicing of cyclin-dependent kinase-associated protein phosphatase KAP increases proliferation and migration in glioblastoma.

The cyclin-dependent kinase (Cdk)-associated protein phosphatase KAP is a dual-specificity phosphatase of which the only known function is to dephosphorylate Cdk2 and inhibit cell cycle progression. Paradoxically, we find increased KAP mRNA expression in malignant astrocytomas, which correlates with increasing histologic grade and decreased patient survival. We have resolved this apparent paradox with the discovery of aberrant KAP splicing in malignant astrocytomas that leads to increased expression of KAP-related transcripts but decreased KAP protein expression. In addition, the aberrant splicing generates a dominant negative KAP variant that increases proliferation. We provide the first evidence that KAP not only regulates proliferation but also inhibits migration by decreasing cdc2 mRNA and protein expression. The effect of KAP on cdc2 expression requires its phosphatase activity but does not involve direct dephosphorylation of cdc2. Thus, KAP regulates both cdc2-dependent migration and Cdk2-dependent proliferation, and its loss due to aberrant splicing increases malignancy in human gliomas.

Alternative Splicing↗
PubMed2006

A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma.

A novel genome-wide screen that combines patient outcome analysis with array comparative genomic hybridization and mRNA expression profiling was developed to identify genes with copy number alterations, aberrant mRNA expression, and relevance to survival in glioblastoma. The method led to the discovery of physical gene clusters within the cancer genome with boundaries defined by physical proximity, correlated mRNA expression patterns, and survival relatedness. These boundaries delineate a novel genomic interval called the functional common region (FCR). Many FCRs contained genes of high biological relevance to cancer and were used to pinpoint functionally significant DNA alterations that were too small or infrequent to be reliably identified using standard algorithms. One such FCR contained the EphA2 receptor tyrosine kinase. Validation experiments showed that EphA2 mRNA overexpression correlated inversely with patient survival in a panel of 21 glioblastomas, and ligand-mediated EphA2 receptor activation increased glioblastoma proliferation and tumor growth via a mitogen-activated protein kinase-dependent pathway. This novel genome-wide approach greatly expanded the list of target genes in glioblastoma and represents a powerful new strategy to identify the upstream determinants of tumor phenotype in a range of human cancers.

Brain Neoplasms↗
PubMed2006

Personal hair dye use and risks of glioma, meningioma, and acoustic neuroma among adults.

Previous studies have suggested an association of personal hair dye use with bladder and hematopoietic cancers. Risks for brain tumors are not well understood. The authors investigated associations between use of synthetic hair dyes and risk of brain tumors in a hospital-based case-control study. The study included adults newly diagnosed with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) between 1994 and 1998 at three urban US hospitals and 799 controls. Odds ratios were estimated and 95% confidence intervals were calculated using unconditional logistic regression. Detailed exposure histories were obtained by interview. There was no consistent pattern of elevated odds ratios for glioma, meningioma, or acoustic neuroma with use or prolonged use of permanent, semipermanent, temporary, or gradual hair dyes. Although use of permanent brown hair dye for 20 or more years was associated with glioma among women, the estimate was imprecise (odds ratio = 3.8, 95% confidence interval: 1.2, 12.5) and was based on just 13 exposed cases; thus, this could be a chance finding. Overall, there was little consistent evidence for an association of synthetic hair dye use with glioma, meningioma, or acoustic neuroma. However, prolonged use of dark-colored permanent dyes warrants further investigation given the high prevalence of hair dyeing.

Adolescent↗
PubMed2006

Human neural stem cells target experimental intracranial medulloblastoma and deliver a therapeutic gene leading to tumor regression.

PURPOSE: Medulloblastoma, a malignant pediatric brain tumor, is incurable in about one third of patients despite multimodal treatments. In addition, current therapies can lead to long-term disabilities. Based on studies of the extensive tropism of neural stem cells (NSC) toward malignant gliomas and the secretion of growth factors common to glioma and medulloblastoma, we hypothesized that NSCs could target medulloblastoma and be used as a cellular therapeutic delivery system. EXPERIMENTAL DESIGN: The migratory ability of HB1.F3 cells (an immortalized, clonal human NSC line) to medulloblastoma was studied both in vitro and in vivo. As proof-of-concept, we used HB1.F3 cells engineered to secrete the prodrug activating enzyme cytosine deaminase. We investigated the potential of human NSCs to deliver a therapeutic gene and reduce tumor growth. RESULTS: The migratory capacity of HB1.F3 cells was confirmed by an in vitro migration assay, and corroborated in vivo by injecting chloromethylbenzamido-Dil-labeled HB1.F3 cells into the hemisphere contralateral to established medulloblastoma in nude mice. In vitro studies showed the therapeutic efficacy of HB1.F3-CD on Daoy cells in coculture experiments. In vitro therapeutic studies were conducted in which animals bearing intracranial medulloblastoma were injected ipsilaterally with HB1.F3-CD cells followed by systemic 5-flourocytosine treatment. Histologic analyses showed that human NSCs migrate to the tumor bed and its boundary, resulting in a 76% reduction of tumor volume in the treatment group (P<0.01). CONCLUSION: These studies show for the first time the potential of human NSCs as an effective delivery system to target and disseminate therapeutic agents to medulloblastoma.

Animals↗
PubMed2006

Survival rates and patterns of care for patients diagnosed with supratentorial low-grade gliomas: data from the SEER program, 1973-2001.

BACKGROUND: Detailed population-based estimates of long-term survival as well as patterns of care for patients with low-grade gliomas examined by age at diagnosis, gender, and race have not been widely available. METHODS: Time to death was examined among 2009 individuals diagnosed with a supratentorial low-grade glioma and reported to the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute from 1973-2001 using Kaplan-Meier estimation. A Cox proportional hazards model was used to assess the effect of age at diagnosis, race, gender, histology, anatomic location within the brain, first course of treatment, and year of diagnosis upon this risk. RESULTS: The cumulative 5-, 10-, 15- and 20-year survival rates among all individuals initially diagnosed with a supratentorial low-grade glioma were 59.9% (95% confidence interval [95% CI], 57.6-62.2); 42.6% (95% CI, 39.9-45.2); 31.9% (95% CI, 29.0-34.8); and 26.0% (95% CI, 22.7-29.2), respectively. Improved survival was significantly associated with female gender (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), younger age, white race (HR, 0.70; 95% CI, 0.54-0.93), histology, and later year of diagnosis. Surgical treatment was associated with increased survival. The use of radiation therapy as a first course of treatment for these lesions has significantly decreased over time with the majority of patients receiving only surgery as a first course of treatment. CONCLUSIONS: Data for patients diagnosed with low-grade gliomas revealed increasing survival times over the past 25 years with a subset of patients surviving for decades. Differences in survival by race, gender, histology, and first course of treatment were appreciated. These data suggested that the clinical course of low-grade glioma for some patients may be more encouraging than previously perceived and that the identification of this group of patients may allow refinement of current treatment protocols.

Adolescent↗
PubMed2006

Targeting of melanoma brain metastases using engineered neural stem/progenitor cells.

Brain metastases are an increasingly frequent and serious clinical problem for cancer patients, especially those with advanced melanoma. Given the extensive tropism of neural stem/progenitor cells (NSPCs) for pathological areas in the central nervous system, we expanded investigations to determine whether NSPCs could also target multiple sites of brain metastases in a syngeneic experimental melanoma model. Using cytosine deaminase-expressing NSPCs (CD-NSPCs) and systemic 5-fluorocytosine (5-FC) pro-drug administration, we explored their potential as a cell-based targeted drug delivery system to disseminated brain metastases. Our results indicate a strong tropism of NSPCs for intracerebral melanoma metastases. Furthermore, in our therapeutic paradigm, animals with established melanoma brain metastasis received intracranial implantation of CD-NSPCs followed by systemic 5-FC treatment, resulting in a significant (71%) reduction in tumor burden. These data provide proof of principle for the use of NSPCs for targeted delivery of therapeutic gene products to melanoma brain metastases.

Animals↗
PubMed2006

Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of adult brain tumors.

Genes involved in phase I and phase II regulation of aromatic hydrocarbon-induced effects exhibit sequence variability that may mediate the risk of adult brain tumors. We evaluated associations between gene variants in CYP1A1, CYP1B1, GSTM3, EPHX1, and NQO1 and adult brain tumor incidence. Cases were patients with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) diagnosed from 1994 to 1998 at three U.S. hospitals. Controls were 799 patients admitted to the same hospitals for nonmalignant conditions. DNA was extracted from blood samples collected from 1277 subjects, and genotyping was conducted for CYP1A1 I462V, CYP1B1 V432L, EPHX1 Y113H, GSTM3 *A/*B (intron 6 deletion), and NQO1 P187S. The CYP1B1 V432L homozygous variant was associated with decreased risk of meningioma (odds ratio [OR] = 0.6; 95% CI, 0.3-1.0) but not the other tumor types. The GSTM3 *B/*B genotype was associated with increased risk of glioma (OR = 2.3; 95% CI, 1.0-5.2) and meningioma (OR = 3.6; 95% CI, 1.3-9.8). Increased risks associated with GSTM3 *B/*B were observed in younger subjects (age < 50) and older subjects (age > or = 50), in men and women, and within each study site. The magnitude of association for GSTM3 with glioma and meningioma was greater among ever-smokers than among those who had never smoked. None of the other genotypes showed consistent associations with any tumor type. The association with the GSTM3 *B allele, while intriguing, requires replication, and additional research is needed to clarify the function of the GSTM3 alleles studied here.

Adult↗
PubMed2006

Supratentorial low-grade glioma resectability: statistical predictive analysis based on anatomic MR features and tumor characteristics.

PURPOSE: To retrospectively assess the main variables that affect the complete magnetic resonance (MR) imaging-guided resection of supratentorial low-grade gliomas. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective HIPAA-compliant study, with the requirement for informed consent waived. Data from 101 patients (61 men, 40 women; mean age, 39 years; age range, 18-72 years) who had nonenhancing supratentorial mass lesions that were histopathologically diagnosed as low-grade (World Health Organization grade II) gliomas and consecutively underwent surgery with intraoperative MR imaging guidance were analyzed. There were 21 low-grade astrocytomas, 64 oligodendrogliomas, and 16 mixed oligoastrocytomas. Initial and residual tumor volumes were measured on intraoperative T2-weighted MR images and three-dimensional spoiled gradient-echo MR images. The anatomic relationships between the tumor and eloquent cortical and/or subcortical regions and the influence of these relationships on the extent of resection were analyzed on the basis of preoperative MR imaging findings. Summary measures, univariate Fisher exact test and t test, and multivariate logistic regression analyses were performed. RESULTS: Tumor volume ranged from 2.7-231.0 mL. Univariate analyses revealed the following tumor characteristics to be significant predictive variables of incomplete tumor resection: diffuse tumor margin on T2-weighted MR images, oligodendroglioma or oligoastrocytoma histopathologic type, and large tumor volume (P < .05 for all). Tumor involvement of the following structures was associated with incomplete resection: corpus callosum, corticospinal tract, insular lobe, middle cerebral artery, motor cortex, optic radiation, visual cortex, and basal ganglia (P < .05 for all). Multivariate analyses revealed that incomplete tumor resection was due to tumor involvement of the corticospinal tract (P < .01), large tumor volume (P < .01), and oligodendroglioma histopathologic type (P = .02). CONCLUSION: The main variables associated with incomplete tumor resection in 101 patients were identified by using statistical predictive analyses.

Adolescent↗
PubMed2006

Lead, genetic susceptibility, and risk of adult brain tumors.

BACKGROUND: Although few etiologic factors for brain tumors have been identified, limited data suggest that lead may increase the risk of brain tumors, particularly meningioma. The ALAD G177C polymorphism affects the toxicokinetics of lead and may confer genetic susceptibility to adverse effects of lead exposure. METHODS: We examined occupational exposure to lead and risk of brain tumors in a multisite, hospital-based, case-control study of 489 patients with glioma, 197 with meningioma, and 799 non-cancer controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to hospital. ALAD genotype was assessed by a Taqman assay for 355 glioma patients, 151 meningioma patients, and 505 controls. Exposure to lead was estimated using a rigorous questionnaire-based exposure assessment strategy incorporating lead measurement and other occupational data abstracted from published articles and reports. RESULTS: Increased risk of meningioma with occupational lead exposure (estimated by odds ratios and 95% confidence intervals) was most apparent in individuals with the ALAD2 variant allele, for whom risk increased from 1.1 (0.3-4.5) to 5.6 (0.7-45.5) and 12.8 (1.4-120.8) for estimated cumulative lead exposures of 1 to 49 microg/m3-y, 50 to 99 microg/m3-y, and >or=100 microg/m3-y, respectively, compared with unexposed individuals (two-sided P trend = 0.06). This relationship became stronger after excluding occupational lead exposures characterized by a low confidence level or occurring in the 10 years before meningioma diagnosis. Occupational lead exposure was not associated with glioma risk. CONCLUSIONS: Although our results indicate that lead may be implicated in meningioma risk in genetically susceptible individuals, these results need to be interpreted with caution given the small numbers of exposed cases with a variant genotype.

Adolescent↗
PubMed2006

Challenges in contemporary academic neurosurgery.

Traditionally, the ideal academic neurosurgeon has been a "quadruple threat," with excellence in clinical work, teaching, research, and administration. This tradition was best exemplified in Harvey Cushing, who developed the field of neurosurgery 90 years ago. This paradigm will probably have to change as academic neurosurgeons face major challenges. In patient care, these include increasing regulatory control, increasing malpractice costs, consolidation of expensive care in academic centers, and decreasing reimbursement; in resident teaching, work hour limitations and a changing resident culture; in research, the increasing dominance of basic scientists in governmental funding decisions and decreased involvement of neurosurgeons in scientific review committees; and in administration, problems of relationships in the workplace, patient safety, and employment compliance in an increasingly bureaucratic system. To meet these challenges, the new academic neurosurgeon will probably not be a quadruple threat personally but will be part of a quadruple threat in a department and institution. Neurosurgeons in such a setting will have to work with hospital, medical school, and national and international groups to address malpractice, reimbursement, subspecialization, and training problems; find supplemental sources of income through grants, development funds, and hospital support; lead in the development of multidisciplinary centers for neuroscience, brain tumor, spine, and other initiatives; and focus on training leaders for hospital, regional, and national groups to reconfigure neurosurgery. Collaboration, flexibility, and leadership will be characteristic of the academic neurosurgeon in this new era.

Academic Medical Centers↗
PubMed2005

PEX-producing human neural stem cells inhibit tumor growth in a mouse glioma model.

A unique characteristic of neural stem cells is their capacity to track glioma cells that have migrated away from the main tumor mass into the normal brain parenchyma. PEX, a naturally occurring fragment of human metalloproteinase-2, acts as an inhibitor of glioma and endothelial cell proliferation, migration, and angiogenesis. In the present study, we evaluated the antitumor activity of PEX-producing human neural stem cells against malignant glioma. The HB1.F3 cell line (immortalized human neural stem cell) was transfected by a pTracer vector with PEX. The retention of the antiproliferative activity and migratory ability of PEX-producing HB1.F3 cells (HB1.F3-PEX) was confirmed in vitro. For the in vivo studies, DiI-labeled HB1.F3-PEX cells were stereotactically injected into established glioma tumor in nude mice. Tumor size was subsequently measured by magnetic resonance imaging and at the termination of the studies by histologic analysis including tumor volume, microvessel density, proliferation, and apoptosis rate. Histologic analysis showed that DiI-labeled HB1.F3-PEX cells migrate at the tumor boundary and cause a 90% reduction of tumor volume (P < 0.03). This reduction in tumor volume in animals treated with HB1.F3-PEX was associated with a significant decrease in angiogenesis (44.8%, P < 0.03) and proliferation (23.6%, P < 0.03). These results support the use of neural stem cells as delivery vehicle for targeting therapeutic genes against human glioma.

Animals↗
PubMed2005

Reproductive and hormonal factors and risk of brain tumors in adult females.

Causes of brain tumors are largely unknown, and there is an urgent need to identify possible risk factors. Several observations point to a possible role of reproductive hormones, but few epidemiologic studies have examined whether reproductive factors, such as age at menarche and parity, are associated with brain tumor risk. We conducted a multi-center case-control study of newly diagnosed glioma (n = 212) and meningioma (n = 151) and frequency-matched controls (n = 436) in women from hospitals in Phoenix, Arizona; Boston, Massachusetts; and Pittsburgh, Pennsylvania between 1994 and 1998. Research nurses interviewed patients regarding potential risk factors for brain tumors, including reproductive factors and hormone use. Unconditional logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Risk of glioma increased with older age at menarche [OR = 1.90 (95% CI = 1.09-3.32) for age at menarche > or =14 vs. <12 years]. Early age at first birth was associated with reduced risk of glioma [OR = 0.43 (95% CI = 0.23-0.83) for a first birth before age 20 vs. nulliparity], but there was little effect of number of births. Exogenous hormone use was also associated with a lower risk of glioma, but risks did not vary systematically according to duration of use or age at first use. Possibly owing to low statistical power, there were few noteworthy associations between meningioma and reproductive factors, other than a nonsignificant (p = 0.09) trend of increasing risk with increasing age at menopause. The findings suggest that hormonal exposures early in life may be associated with risk of glioma, but the evidence is inconsistent and does not point clearly to a specific causal or protective hypothesis.

Adolescent↗
PubMed2005

Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance.

BACKGROUND: No age-adjusted or histologic-adjusted assessments of the association between extent of resection and risk of either recurrence or death exist for neurosurgical patients who undergo resection of low-grade glioma using intraoperative magnetic resonance image (MRI) guidance. METHODS: The current data included 156 patients who underwent surgical resection of a unifocal, supratentorial, low-grade glioma in the MRI suite at Brigham and Women's Hospital between January 1, 1997, and January 31, 2003. Estimates of disease-free and overall survival probabilities were calculated using Kaplan-Meier methodology. The association between extent of resection and these probabilities was measured using a Cox proportional hazards model. Observed death rates were compared with the expected death rate using age-specific and histologic-specific survival rates obtained from the Surveillance, Epidemiology, and End Results Registry. RESULTS: Patients who underwent subtotal resection were at 1.4 times the risk of disease recurrence (95% confidence interval [95% CI], 0.7-3.1) and at 4.9 times the risk of death (95% CI, 0.61-40.0) relative to patients who underwent gross total resection. The 1-year, 2-year, and 5-year age-adjusted and histologic-adjusted death rates for patients who underwent surgical resection using intraoperative MRI guidance were 1.9% (95% CI, 0.3-4.2%), 3.6% (95% CI, 0.4-6.7%), and 17.6% (95% CI, 5.9-29.3%), respectively: significantly lower than the rates reported using national data bases. CONCLUSIONS: The data from the current study suggested a possible association between surgical resection and survival for neurosurgical patients who underwent surgery for low-grade glioma under intraoperative MRI guidance. Further study within the context of a large, prospective, population-based project will be needed to confirm these findings.

Adult↗
PubMed2005

Self-reported electrical appliance use and risk of adult brain tumors.

Electrical appliances produce the highest intensity exposures to residential extremely low frequency electromagnetic fields. The authors investigated whether appliances may be associated with adult brain tumors in a hospital-based case-control study at three centers in the United States from 1994 to 1998. A total of 410 glioma, 178 meningioma, and 90 acoustic neuroma cases and 686 controls responded to a self-administered questionnaire about 14 electrical appliances. There was little evidence of association between brain tumors and curling iron, heating pad, vibrating massager, electric blanket, heated water bed, sound system, computer, television, humidifier, microwave oven, and electric stove. Ever use of hair dryers was associated with glioma (odds ratio = 1.7, 95% confidence interval: 1.1, 2.5), but there was no evidence of increasing risk with increasing amount of use. In men, meningioma was associated with electric shaver use (odds ratio = 10.9, 95% confidence interval: 2.3, 50), and odds ratios increased with cumulative minutes of use, although they were based on only two nonexposed cases. Recall bias for appliances used regularly near the head or chance may provide an alternative explanation for the observed associations. Overall, results indicate that extremely low frequency electromagnetic fields from commonly used household appliances are unlikely to increase the risk of brain tumors.

Adolescent↗
PubMed2005

Statistical validation of brain tumor shape approximation via spherical harmonics for image-guided neurosurgery.

RATIONALE AND OBJECTIVES: Surgical planning now routinely uses both two-dimensional (2D) and three-dimensional (3D) models that integrate data from multiple imaging modalities, each highlighting one or more aspects of morphology or function. We performed a preliminary evaluation of the use of spherical harmonics (SH) in approximating the 3D shape and estimating the volume of brain tumors of varying characteristics. MATERIALS AND METHODS: Magnetic resonance (MR) images from five patients with brain tumors were selected randomly from our MR-guided neurosurgical practice. Standardized mean square reconstruction errors (SMSRE) by tumor volume were measured. Validation metrics for comparing performances of the SH method against segmented contours (SC) were the dice similarity coefficient (DSC) and standardized Euclidean distance (SED) measure. RESULTS: Tumor volume range was 22,413-85,189 mm3, and range of number of vertices in triangulated models was 3674-6544. At SH approximations with degree of at least 30, SMSRE were within 1.66 x 10(-5) mm(-1). Summary measures yielded a DSC range of 0.89-0.99 (pooled median, 0.97 and significantly >0.7; P < .001) and an SED range of 0.0002-0.0028 (pooled median, 0.0005). CONCLUSION: 3D shapes of tumors may be approximated by using SH for neurosurgical applications.

Adult↗
PubMed2005

A low-field intraoperative MRI system for glioma surgery: is it worthwhile?

As intraoperative MRI expands its presence, its use will undoubtedly increase in glioma surgery. The foregoing discussion makes it clear that its benefits are unsurpassed by any other existing system. Because of their radiographic characteristics and gross appearance, gliomas are particularly suited for intraoperative MRI-guided surgery. It enables us to localize gliomas and define tumor margins precisely when, during surgery, the difference between tumor and brain is not easy to discern. The images generated during surgery serve as a detailed and updated map within which navigation is performed with utmost precision. Its significance is further highlighted when dealing with tumors in eloquent areas of the brain, where uncertainties over the location of tumor in relation to important brain structures can hinder the removal of tumor. By providing accurate positional information and in conjunction with cortical mapping techniques, intraoperative MRI enhances the confidence of the surgeon to go forward with resection or to stop when reaching important cortex. It allows us to perform the resection to the desired limit without causing injury to nearby important structures, thereby preventing postoperative neurologic deficits. The tracking system guides us in targeting each minute part of the tumor with unprecedented accuracy, and the ability to update images makes possible the constant evaluation of the progress of surgery. This near-real-time imaging can eliminate the errors brought about by the brain shifting that occurs throughout surgery. It also serves the important purpose of verifying the presence and position of any remaining tumor in the operative field. By means of sequential imaging, additional resection can be performed on any remaining tumor until imaging shows completion. The unwanted occurrence of finding residual tumor on a postoperative scan is thus practically eliminated. As a result, the surgical goal of complete or optimal resection can be achieved without any guesswork. Ultimately, what this means for the glioma patient is increased likelihood of longer survival brought about by a more thorough tumor resection. Intraoperative MRI addresses many of the surgical challenges posed by gliomas. As it becomes more available, there will come a point when the prevailing persuasion will be that some poorly defined tumors near eloquent cortex should not be operated on without intraoperative MRI. In the final analysis, not only is intraoperative MRI worthwhile but it will, in all likelihood, become a standard of care for many glioma cases.

Brain Neoplasms↗
PubMed2005

Metacognition and false recognition in patients with frontal lobe lesions: the distinctiveness heuristic.

The distinctiveness heuristic is a response mode in which participants expect to remember vivid details of an experience and make recognition decisions based on this metacognitive expectation. Whereas much is known about the cognitive processes that are involved in using the distinctiveness heuristic, little is known about the corresponding brain processes. Because such metacognitive processes that involve the evaluation and control of one's memory are believed to be dependent upon the frontal lobes, the authors examined whether the distinctiveness heuristic could be engaged to reduce false recognition in a repetition lag paradigm in patients with lesions of their frontal lobes. Half of the participants studied pictures and corresponding auditory words; the other half studied visual and auditory words. Studied and novel items were presented at test as words only, with all novel items repeating after varying lags. Controls who studied pictures were able to reduce their false recognition of repeated lag items relative to those controls who studied words, demonstrating their use of the distinctiveness heuristic. Patients with frontal lobe lesions showed similar levels of false recognition regardless of whether they studied pictures and words or words only, suggesting that they were unable to use the distinctiveness heuristic. The authors suggest that the distinctiveness heuristic is a metacognitive strategy, dependent upon the frontal lobes, that may be engaged by healthy individuals to reduce their false recognition.

Adult↗