Scientific Misconduct.

Scientific misconduct has been defined as fabrication, falsification, and plagiarism. Scientific misconduct has occurred throughout the history of science. The US government began to take systematic interest in such misconduct in the 1980s. Since then, a number of studies have examined how frequently individual scientists have observed scientific misconduct or were involved in it. Although the studies vary considerably in their methodology and in the nature and size of their samples, in most studies at least 10% of the scientists sampled reported having observed scientific misconduct. In addition to studies of the incidence of scientific misconduct, this review considers the recent increase in paper retractions, the role of social media in scientific ethics, several instructional examples of egregious scientific misconduct, and potential methods to reduce research misconduct.

Adult separation anxiety in treatment nonresponders with anxiety disorders: delineation of the syndrome and exploration of attachment-based psychotherapy and biomarkers.

Clinically significant separation anxiety [SA] has been identified as being common among patients who do not respond to psychiatric interventions, regardless of intervention type (pharmacological or psychotherapeutic), across anxiety and mood disorders. An attachment formation and maintenance domain has been proposed as contributing to anxiety disorders. We therefore directly determined prevalence of SA in a population of adult treatment non-responders suffering from primary anxiety. In these separation anxious nonresponders, we pilot-tested an SA-focused, attachment-based psychotherapy for anxiety, Panic-Focused Psychodynamic Psychotherapy-eXtended Range [PFPP-XR], and assessed whether hypothesized biomarkers of attachment were engaged. We studied separation anxiety [SA] in 46 adults (ages 23-70 [mean 43.9 (14.9)]) with clinically significant anxiety symptoms (Hamilton Anxiety Rating Scale [HARS]≥15), and reporting a history of past non-response to psychotherapy and/or medication treatments. Thirty-seven (80%) had clinically significant symptoms of separation anxiety (Structured Clinical Interview for Separation Anxiety Symptoms [SCI-SAS] score≥8). Five of these subjects completed an open clinical trial of Panic Focused Psychodynamic Psychotherapy eXtended Range [PFPP-XR], a 21-24 session, 12-week manualized attachment-focused anxiolytic psychodynamic psychotherapy for anxiety. Patients improved on "adult threshold" SCI-SAS (current separation anxiety) (p=.016), HARS (p=0.002), and global severity, assessed by the Clinical Global Impression Scale (p=.0006), at treatment termination. Salivary oxytocin levels decreased 67% after treatment (p=.12). There was no significant change in high or low frequency HRV after treatment, but change in high frequency HRV inversely correlated with treatment change in oxytocin (p<.02), and change in low frequency HRV was positively associated with change in oxytocin (p<.02). SA is surprisingly prevalent among non-responders to standard anti-anxiety treatments, and it may represent a novel transdiagnostic target for treatment intervention in this population. Anxiety and global function improved in a small trial of a brief, manualized, attachment-focused psychodynamic psychotherapy, potentially supporting the clinical relevance of attachment dysfunction in this sample. The large decrease in oxytocin levels with treatment, although not statistically significant in this very small sample, suggests the need for further study of oxytocin as a putative biomarker or mediator of SA response. These pilot data generate testable hypotheses supporting an attachment domain underlying treatment-resistant anxiety, and new treatment strategies.

Some revolutions in neuroscience.

In the long history of the study of the nervous system, there have been a number of major developments that involved radical and permanent changes in fundamental beliefs and assumptions about the nervous system and in tactics and strategies for studying it. These may be termed Revolutions in Neuroscience. This essay considers eight of these, ranging from the 6th century BCE to the end of the 20th century.

Three before their time: neuroscientists whose ideas were ignored by their contemporaries.

I discuss three examples of neuroscientists whose ideas were ignored by their contemporaries but were accepted as major insights decades or even centuries later. The first is Emanuel Swedenborg (1688-1772) whose ideas on the functions of the cerebral cortex were amazingly prescient. The second is Claude Bernard (1813-1878) whose maxim that the constancy of the internal environment is the condition for the free life was not understood for about 50 years when it came to dominate the development of modern physiology. The third is Joseph Altman (1925-) who overturned the traditional dogma that no new neurons are made in the adult mammalian brain and was vindicated several decades later.

Single neuron studies of inferior temporal cortex.

This paper reviews our experiments on the response properties of single neurons in inferior temporal (IT) cortex in the monkey that were carried out starting in 1965. It describes situational factors that led us to find neurons sensitive to images of faces and hands and summarizes the basic sensory properties of IT neurons. Subsequent developments on the cognitive properties of IT neurons and on imaging the responses of human temporal cortex to facial images are outlined. Finally, this paper summarizes recent results on fMRI imaging of the responses of temporal cortex to facial images.

Endoscopic localization of the anterior and posterior ethmoid arteries.

OBJECTIVES: Understanding the endoscopic locations of the anterior and posterior ethmoid arteries is important during endoscopic sinus or endoscopic skull base procedures so that these arteries can be avoided. Therefore, the objective of this study was to define the endoscopic locations of the ethmoid arteries. METHODS: Twenty-four cadaver heads were used to identify the endoscopic location of the ethmoid arteries via an external incision. An image guidance system was used to record the locations of these arteries. The anterior ethmoid artery was referenced to the axilla of the middle turbinate, and the posterior ethmoid artery to the anterior wall of the sphenoid sinus. The closest lamella to these arteries was identified. RESULTS: Forty-eight nasal cavities were dissected. The mean distance from the axilla to the anterior ethmoid artery was 17.5 mm. The anterior ethmoid artery was located immediately anterior to (31%), at (36%), or immediately posterior to (33%) the superior attachment of the basal lamella. The mean distance from the posterior ethmoid artery to the anterior ethmoid artery was 14.9 mm. The mean distance from the posterior ethmoid artery to the anterior wall of the sphenoid sinus was 8.1 mm. The posterior ethmoid artery was either anterior to (98%) or at (2%) the anterior face of the sphenoid sinus. CONCLUSIONS: Specific endoscopic anatomic relationships and measurements have been presented for the anterior and posterior ethmoid arteries.

Cocaine- and opiate-related fatal overdose in New York City, 1990-2000.

BACKGROUND: In New York City (NYC), the annual mortality rate is higher for accidental drug overdoses than for homicides; cocaine and opiates are the drugs most frequently associated with drug overdose deaths. We assessed trends and correlates of cocaine- and opiate-related overdose deaths in NYC during 1990-2000. METHODS: Data were collected from the NYC Office of the Chief Medical Examiner (OCME) on all fatal drug overdoses involving cocaine and/or opiates that occurred between 1990-2000 (n = 8,774) and classified into three mutually exclusive groups (cocaine only; opiates-only; cocaine and opiates). Risk factors for accidental overdose were examined in the three groups and compared using multinomial logistic regression. RESULTS: Overall, among decedents ages 15-64, 2,392 (27.3%) were attributed to cocaine only and 2,825 (32.2%) were attributed to opiates-only. During the interval studied, the percentage of drug overdose deaths attributed to cocaine only fell from 29.2% to 23.6% while the percentage of overdose deaths attributed to opiates-only rose from 30.6% to 40.1%. Compared to New Yorkers who fatally overdosed from opiates-only, fatal overdose attributed to cocaine-only was associated with being male (OR = 0.71, 95% CI 0.62-0.82), Black (OR = 4.73, 95% CI 4.08-5.49) or Hispanic (OR = 1.51, 95% CI 1.29-1.76), an overdose outside of a residence or building (OR = 1.34, 95% CI 1.06-1.68), having alcohol detected at autopsy (OR = 0.50, 95% CI 0.44-0.56) and older age (55-64) (OR = 2.53 95% CI 1.70-3.75)). CONCLUSION: As interventions to prevent fatal overdose become more targeted and drug specific, understanding the different populations at risk for different drug-related overdoses will become more critical.

Initial surgical treatment for chronic frontal sinusitis: a pilot study.

OBJECTIVES: The initial surgical treatment for chronic frontal sinusitis is not well defined. Our objective was to determine the effectiveness of anterior ethmoidectomy for chronic frontal sinusitis. METHODS: Patients with chronic frontal sinusitis who underwent anterior ethmoidectomy as initial surgical treatment were reviewed. Data were collected from computed tomography scans with use of the Lund-Mackay scale. Data on demographics, comorbidities, management, postoperative recovery, and follow-up were collected. RESULTS: Seventy-seven patients representing 121 diseased frontal sinuses met the inclusion criteria. The respiratory comorbidities were asthma alone (8.3%), asthma and polyps (6.6%), aspirin triad (5.8%), and cystic fibrosis (0.8%). Nineteen of 121 frontal sinuses (15.7%) belonged to smokers. Fourteen of 121 frontal sinuses (11.5%) exhibited postoperative evidence of disease. Of these 14 frontal sinuses, 10 (8.3%) underwent revision surgery. Frontal sinuses of patients with aspirin triad, with both nasal polyposis and asthma, or with inter-frontal sinus septal cells were more likely to fail Draf I surgery (p < .05). CONCLUSIONS: Anterior ethmoidectomy for drainage of frontal sinuses appears to be effective initial surgical treatment for chronic frontal sinusitis. Patients with aspirin triad, both asthma and polyposis, or inter-frontal sinus septal cells are more likely to fail this procedure.

Tornwaldt's cyst: incidence and a case report.

Tornwaldt's cyst is an uncommon type of nasopharyngeal cyst that may cause clinically significant symptoms. We reviewed reports of 31,855 computed tomography (CT) scans and 21,158 magnetic resonance imaging (MRI) scans to ascertain how many Tornwaldt's cysts were discovered incidentally. These images had been obtained between Jan. 1, 1994, and Dec. 31, 1999, at the University of Virginia Health Sciences Center. We found that 32 Tornwaldt's cysts had been incidentally detected in 20 women and 12 men. Four of these cysts had been found on CT (0.013%; mean size: 0.66 cm3) and 28 on MRI (0.13%; mean size: 0.58 cm3). The overall rate was 0.06% (32/53,013). The most common indications for imaging in these patients were headache, seizures, dizziness/vertigo, and pharyngeal symptoms. We also report the case of a patient with a symptomatic Tornwaldt's cyst whose symptoms resolved after treatment with endoscopic marsupialization. Tornwaldt's cyst should be remembered as an uncommon but potentially treatable cause of many symptoms seen in a typical otolaryngology practice.

The discovery of motor cortex and its background.

In 1870 Gustav Fritsch and Edvard Hitzig showed that electrical stimulation of the cerebral cortex of a dog produced movements. This was a crucial event in the development of modern neuroscience because it was the first good experimental evidence for a) cerebral cortex involvement in motor function, b) the electrical excitability of the cortex, c) topographic representation in the brain, and d) localization of function in different regions of the cerebral cortex. This paper discusses their experiment and some developments in the previous two centuries that led to it including the ideas of Thomas Willis and Emanuel Swedenborg, the widespread interest in electricity and the localizations of function of Franz Joseph Gall, John Hughlings Jackson, and Paul Broca. We also consider the subsequent study of the motor cortex by David Ferrier and others.

Quantitative investigation of connections of the prefrontal cortex in the human and macaque using probabilistic diffusion tractography.

The functions of prefrontal cortex (PFC) areas are constrained by their anatomical connections. There is little quantitative information about human PFC connections, and, instead, our knowledge of primate PFC connections is derived from tracing studies in macaques. The connections of subcortical areas, in which white matter penetration and hence diffusion anisotropy are greatest, can be studied with diffusion-weighted imaging (DWI) tractography. We therefore used DWI tractography in four macaque and 10 human hemispheres to compare the connections of PFC regions with nine subcortical regions, including several fascicles and several subcortical nuclei. A distinct connection pattern was identified for each PFC and each subcortical region. Because some of the fascicles contained connections with posterior cortical areas, it was also possible to draw inferences about PFC connection patterns with posterior cortical areas. Notably, it was possible to identify similar circuits centered on comparable PFC regions in both species; PFC regions probably engage in similar patterns of regionally specific functional interaction with other brain areas in both species. In the case of one area traditionally assigned to the human PFC, the pars opercularis, the distribution of connections was not reminiscent of any macaque PFC region but, instead, resembled the pattern for macaque ventral premotor area. Some limitations to the DWI approach were apparent; the high diffusion anisotropy in the corpus callosum made it difficult to compare connection probability values in the adjacent cingulate region.

Limits of endoscopic visualization and instrumentation in the frontal sinus.

BACKGROUND: Endoscopic limitations in the frontal sinus are poorly defined. We set out to define these limits. METHODS: Fifteen cadaveric heads underwent endoscopic frontal sinusotomies (Draf IIA, IIB, III). Areas of frontal sinus openings were calculated. Coordinates of the most distant points for instrumentation, visualization, and instrumentation with visualization in the frontal sinus were identified with the use of image guidance. RESULTS: Twenty-eight frontal sinuses were evaluated. The mean sinus opening areas were 47.5 mm2, 105.1 mm2, and 246.4 mm2 for Draf IIA, IIB, and III. Visualization exceeds instrumentation and visualized reach (P<0.05) regardless of different frontal sinusotomies. Anterior and lateral instrumentation and visualized reach increase as the frontal sinus opening increases (PIIB>IIA (P<0.04). There is no statistical difference for superior visualization, instrumentation, and visualized reach among various sinusotomies (P>0.05). CONCLUSIONS: Endoscopic visualization exceeds instrumentation and instrumentation exceeds visualized reach. Enlarging frontal sinus opening area increases instrumentation and visualization.

A golden experience: Fifty years of experience managing the frontal sinus.

OBJECTIVES/HYPOTHESIS: The frontal sinus is one of the most anatomically complex and inaccessible of the paranasal sinuses. As a result, surgeons have continually tried to improve surgical management of the frontal sinus. The senior author (c.w.g.) shares 50 years of experience managing the frontal sinus. DATA SOURCES: PubMed literature search. REVIEW METHODS: Review of the literature regarding landmark innovations in frontal sinus surgery. RESULTS: Open approaches established that the frontal sinus is accessible, and in certain circumstances, such as with large osteoma or papilloma, are still required. The endoscope changed the surgical landscape and allowed for greater finesse and decreased morbidity. Sinus balloon dilation is the newest change in frontal sinus management and shows promise in properly selected cases. CONCLUSION: Surgery of the frontal sinus continues to evolve and improve. Although there are new techniques, the older techniques are still pertinent.

Psychotherapies for Panic Disorder: A Tale of Two Sites.

OBJECTIVE: To compare cognitive-behavioral therapy (CBT), panic-focused psychodynamic psychotherapy (PFPP), and applied relaxation training (ART) for primary DSM-IV panic disorder with and without agoraphobia in a 2-site randomized controlled trial. METHOD: 201 patients were stratified for site and DSM-IV agoraphobia and depression and were randomized to CBT, PFPP, or ART (19-24 sessions) over 12 weeks in a 2:2:1 ratio at Weill Cornell Medical College (New York, New York) and University of Pennsylvania ("Penn"; Philadelphia, Pennsylvania). Any medication was held constant. RESULTS: Attrition rates were ART, 41%; CBT, 25%; and PFPP, 22%. The most symptomatic patients were more likely to drop out of ART than CBT or PFPP (P = .013). Outcome analyses revealed site-by-treatment interactions in speed of Panic Disorder Severity Scale (PDSS) change over time (P = .013). At Cornell, no differences emerged on improvement on the primary outcome, estimated speed of change over time on the PDSS; at Penn, ART (P = .025) and CBT (P = .009) showed greater improvement at treatment termination than PFPP. A site-by-treatment interaction (P = .016) for a priori-defined response (40% PDSS reduction) showed significant differences at Cornell: ART 30%, CBT 65%, PFPP 71% (P = .007), but not at Penn: ART 63%, CBT 60%, PFPP 48% (P = .37). Penn patients were more symptomatic, differed demographically from Cornell patients, had a 7.2-fold greater likelihood of taking medication, and had a 28-fold greater likelihood of taking benzodiazepines. However, these differences did not explain site-by-treatment interactions. CONCLUSIONS: All treatments substantially improved panic disorder with or without agoraphobia, but patients, particularly the most severely ill, found ART less acceptable. CBT showed the most consistent performance across sites; however, the results for PFPP showed the promise of psychodynamic psychotherapy for this disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00353470.

Methods for functional magnetic resonance imaging in normal and lesioned behaving monkeys.

Methods for performing functional magnetic resonance imaging (fMRI) studies in behaving and lesioned monkeys using a human MR scanner are reported. Materials for head implant surgery were selected based on tests for magnetic susceptibility. A primate chair with a rigid head fixation system and a mock scanner environment for training were developed. To perform controlled visual studies, monkeys were trained to maintain fixation for several minutes using a novel training technique that utilized continuous juice rewards. A surface coil was used to acquire anatomical and functional images in four monkeys, one with a partial lesion of striate cortex. High-resolution anatomical images were used after non-uniform intensity correction to create cortical surface reconstructions of both lesioned and normal hemispheres. Our methods were confirmed in two visual experiments, in which functional activations were obtained during both free viewing and fixation conditions. In one experiment, face-selective activity was found in the fundus and banks of the superior temporal sulcus and the middle temporal gyrus in monkeys viewing pictures of faces and objects while maintaining fixation. In a second experiment, regions in occipital, parietal, and frontal cortex were activated in lesioned and normal animals viewing a cartoon movie. Importantly, in the animal with the striate lesion, fMRI signals were obtained in the immediate vicinity of the lesion. Our results extend those previously reported by providing a detailed account of the technique and by demonstrating the feasibility of fMRI in monkeys with lesions.

Processing the facial image: a brief history.

The study of the neural basis of face perception is a major research interest today. This review traces its roots in monkey neuropsychology and neurophysiology beginning with the Klüver-Bucy syndrome and its fractionation and then continuing with lesion and single neuron recording studies of inferior temporal cortex. The context and consequence of the discovery of inferior temporal neurons selective for faces is described and current lines of research on inferior temporal cortex and face processing in both monkeys and humans are outlined.

Genealogy of the "grandmother cell".

A "grandmother cell" is a hypothetical neuron that responds only to a highly complex, specific, and meaningful stimulus, such as the image of one's grandmother. The term originated in a parable Jerry Lettvin told in 1967. A similar concept had been systematically developed a few years earlier by Jerzy Konorski who called such cells "gnostic" units. This essay discusses the origin, influence, and current status of these terms and of the alternative view that complex stimuli are represented by the pattern of firing across ensembles of neurons.

Twitches versus movements: a story of motor cortex.

Modern study of the neurophysiology of the cerebral cortex began with Fritsch and Hitzig's discovery that electrical stimulation of the cortex produces movements. The importance of this discovery was threefold: it was the first demonstration of cortex devoted to motor function, the first indication that the cortex was electrically excitable, and the first evidence of a topographically organized representation in the brain. Fritsch and Hitzig's basic findings were soon replicated by Ferrier, but there were differences between the two studies in both method and interpretation. These different approaches have continued to reverberate in research on the function of motor cortex from the late 19th century to the present day.

Response latencies of neurons in visual areas MT and MST of monkeys with striate cortex lesions.

Cortical area, MT (middle temporal area) is specialized for the visual analysis of stimulus motion in the brain. It has been suggested [Brain 118 (1995) 1375] that motion signals reach area MT via two dissociable routes, namely a 'direct' route which bypasses primary visual cortex (area, striate cortex (V1)) and is specialized for processing 'fast' motion (defined as faster than 6 degrees/s) with a relatively short latency, and an 'indirect' route via area V1 for processing 'slow' motion (slower than 6 degrees/s) with a relatively long latency. We tested this proposal by measuring the effects of unilateral V1 lesions on the magnitudes and latencies of responses to fast- and slow-motion (depicted by random dot kinematograms (RDK) ) of single neurons in areas MT and medial superior temporal area (MST) of anaesthetized macaque monkeys. In the unlesioned hemisphere contralateral to a V1 lesion, response magnitudes and latencies of MT neurons were similar to those previously reported from MT neurons in normal monkeys, and there was no significant association between slow movement and long response latency (>100 ms), or between fast movement and short latency (< or =100 ms). V1 lesions led to diminished response magnitudes and increased latencies in area MT of the lesioned hemisphere, but did not selectively abolish MT responses to slow moving stimuli, or abolish long-latency responses to either slow- or fast-moving stimuli. Response magnitudes and latencies in area MST, which receives visual inputs directly from area MT and is also specialized for visual analysis of motion, were unaffected by V1 lesions (though we have shown elsewhere that directionally-selective responses in both areas were impaired by V1 lesions). Overall, the results are incompatible with the hypothesis that there are dissociable routes to MT specialized for processing separately fast and slow motion.