Human papillomavirus genotype distribution in head and neck cancer: Informing developing strategies for cancer prevention, diagnosis, treatment and surveillance.

Current clinical practice algorithms for HPV testing make no effort to discern the impact of genotypes for patients with head and neck squamous cell carcinoma (HNSC). Data was collected for all patients with HNSCs that had undergone HPV testing at an academic hospital as part of clinical care (2012-2019). Screening was performed using real-time PCR targeting L1 of low and high-risk HPV types, followed by genotyping of positive cases. Genotype status was correlated with age, site and histologic parameters. Of the 964 patients tested, 68% had HPV-positive cancers. Most arose from the oropharynx (OP) (89%) and sinonasal tract (5%). The most frequent genotype was 16 (84.4%) followed by 35 (5.6%), 33 (4.1%), 18 (2.7%), 45 (1.1%), 69 (0.8%) and others (1.3%). There was an association between genotype (16 vs non-16) and tumor origin (OP vs non-OP) (p < 0.0001). HPV18 was associated with transformation to an aggressive small cell phenotype, but HPV16 was not (22% vs 0%, p < 0.0001). Patients with HPV-non-16 OP carcinomas were older than patients with HPV16 OP carcinomas, but the difference was not significant. HPV genotypes are variable and unevenly distributed across anatomic sites of the head and neck. The association of HPV18 with small cell transformation suggests that variants can track with certain phenotypes in ways that may account for differences in clinical behavior. This study challenges the prevailing assumption of HPV equivalency across all high-risk genotypes in ways that may inform preventive, diagnostic, therapeutic and surveillance strategies.

Associations of family characteristics with perceptions of care among parents of children with autism.

BACKGROUND: Although autism spectrum disorder (ASD) is an increasingly common chronic disability, primary care provider (PCPs) report deficits in providing primary care for children with ASD, and parents report lapses in receipt of medical home services. In this study, we describe parental experiences with specific medical home components for their children with ASD. METHODS: We analysed data from all children within the National Survey of Children with Special Health Care Needs database with ASD and a usual place for care (n = 2859). We evaluated the receipt of core medical home components: accessible, comprehensive, coordinated, family centred and compassionate and culturally sensitive care. RESULTS: Children were mean age 10.1 years, and respondents were 75% mothers and 95% reported having a primary care provider (PCP). Seventy-one percent reported care to be usually comprehensive, over three-fourths of respondents reported care to be family centred and compassionate and 87% reported care to be culturally sensitive. Of the parents who reported a need for care coordination (n = 1049), only 14% of parents reported usually getting the help they needed. More educated, English-speaking, non-Hispanic White mothers of older children supported by private insurance were more likely to report never getting as much help coordinating care as desired. Coordination with education services are especially important for children with ASD, yet 27% of parents reported dissatisfaction with PCPs' communication with schools or early intervention. CONCLUSION: Although parents report a high level of access to PCPs and places for care as well as receiving most core components of the medical home, care coordination activities are lacking for children with ASD. More resourced families are particularly likely to report unmet needs.

Involvement of single unit activity in inferotemporal and perirhinal cortices in recognition memory of visual objects in the macaque.

Recognizing objects from the past is a vitally important ability for everyday live. The studies of brain mechanisms responsible for visual recognition memory suggest that the modulation of single unit activity in the inferotemporal and perirhinal cortices could be an important part of the neuronal substrate of recognition memory. In this review, I will describe Stimulus Specific Adaptation (SSA)--the reduction in neuronal response to previously viewed objects. The experimental tasks in which SSA is observed will be presented, along with the possibility that SSA may be enhanced by saccadic exploration of visual scene. Next, I will demonstrate that under special circumstances (partially split-brain preparation) monkeys could recognize the re-presentation of visual images without the concomitant appearance of SSA. The most promising alternative candidate for neuronal mechanism involved in recognition memory is delay activity--an increased frequency of cell firing in the time between the initial presentation of an image and its subsequent re-presentation. In order to determine if delay activity is important for recognition we have started to investigate the effects on recognition memory of disrupting delay activity by electrical stimulation. Preliminary results indicate a positive correlation between a reduction in delay activity and a decrease in recognition performance.

Activity linked to externally cued saccades in single units recorded from hippocampal, parahippocampal, and inferotemporal areas of macaques.

We studied whether target-directed, externally commanded saccadic eye movements (saccades) induced activity in single units in inferotemporal cortex, the hippocampal formation, and parahippocampal gyrus. The monkeys first were required to fix their gaze on a small cross presented to the left or right of center on the monitor screen. The cross was extinguished, and a random 600-1,000 ms thereafter, a small dot was presented for 200 ms. The dot was located either 10 degrees above, below, right, or left of the position on which the fixation cross had been. The monkey made a saccadic eye movement to this dot (in darkness). The neuronal activity around this goal-directed saccade was analyzed. In addition, control conditions were imposed systematically in which similar dots were presented, but the monkey's task was to withhold the saccade. We recorded 290 units from two monkeys. From this group, 134 met two criteria, they did not show visual response in control trials and they had spike rates >2 Hz. These were analyzed further; 53% (71/134) showed modulation related to the target directed saccade, and 29% (39/134) showed saccadic modulation during spontaneous eye movements. These two groups were correlated only weakly. Of the units with significant saccadic modulation, 17% (12/71) showed significant directional selectivity, and 13% (9/71) showed significant position selectivity (P < 0.01). At a lower criterion (P < 0.05), almost one-half (33/71) showed one or the other spatial selectivity. Primates use saccades to acquire visual information. The appearance of strong saccadic modulation in brain structures previously characterized as mnemonic suggests the possibility that the mnemonic circuitry uses an extraretinal signal linked to saccades to control visual memory processes, e.g., synchronizing mnemonic processes to the pulsatile visual data inflow.

Saccadic eye movements, even in darkness, generate event-related potentials recorded in medial sputum and medial temporal cortex.

Saccadic eye movements (saccades) in primates organize the visual information about the environment into a pulsatile course. Recent studies from our laboratory have found substantial single unit activity, of extra-retinal origin, in medial temporal and inferotemporal cortex with each saccade (even in the dark). In the current experiment we studied event-related potentials to spontaneous saccades from electrodes in medial temporal cortex as well as medial septum. Significant event-related potentials were recorded in both regions (again even in the dark). These data suggest that higher-level processing itself may synchronize with saccades.

Mnemonic responses of single units recorded from monkey inferotemporal cortex, accessed via transcommissural versus direct pathways: a dissociation between unit activity and behavior.

Three macaques were trained on a task in which a sequence of single visual images was presented serially, and the monkeys signaled whether the image was a new or a repeated one. The optic chiasm and splenium of the corpus callosum were transected, leaving the anterior commissure as the only path for cortical interhemispheric transfer. Images were presented to only one eye at a time. Re-presentations of images to the same eye were recognized correctly in >95% of trials. A robust stimulus-specific adaptation (i.e., a reduced response to a repeated image) was seen in the population of single units recorded from inferotemporal cortex during these same trials. When an interhemispheric transfer was demanded of the animals (i.e., the re-presentation was made to the other eye), recognition performance was somewhat reduced, to 86% correct. Interestingly, in this situation the stimulus-specific adaptation disappeared completely. The disappearance occurred regardless of whether the transfer direction was from the hemisphere ipsilateral to the recording site to the hemisphere contralateral to the recording site, or vice versa. Thus, stimulus-specific adaptation in inferotemporal cortex units is not required for recognition.

Stimulus specific adaptation in excited but not in inhibited cells in inferotemporal cortex of macaque.

Many cells in inferotemporal cortex respond more actively to a novel presentation than to a subsequent re-presentation of the same image, exhibiting stimulus specific adaptation (SSA). Previously, analysis of this adaptation was limited to visually excited cells, excluding visually inhibited cells. In the present experiment we studied 654 cells in four macaques performing visual tasks. Strong SSA (P < 0.0001) was observed in those cells which were excited by visual stimuli. This adaptation was also seen in the subset of such cells which, though excited by visual stimuli, failed to show visual specificity in their responses. Interestingly, no SSA (P > 0.1) was observed in the group of cells inhibited by visual stimuli. Furthermore, most inhibited cells failed to show visual specificity. This lack of visual specificity and SSA suggests that the visually inhibited cells have a limited role in the detailed information processing of visual perception and memory activated by the tasks used in the present experiments.

Eye movements modulate activity in hippocampal, parahippocampal, and inferotemporal neurons.

1. Inferotemporal, hippocampal, and parahippocampal units were recorded while monkeys were alert (as judged by eye movements) but resting, in both light and dark. 2. Spontaneous saccadic eye movements produced significant changes in unit activity for 108 of 308 cells. This activity is shown to be extraretinal either because it occurred in complete darkness or because of its timing relative to the eye movement. 3. The total saccadic modulation in the ventral temporal lobe is estimated to be over ten million action potentials.

Investigation of long-term recognition and association memory in unit responses from inferotemporal cortex.

We investigated recognition and association memory in the responses of single units isolated in the inferior temporal cortex of a macaque while it performed a visual discrimination task. The unit responses showed significant recognition memory (a decreased response upon image repetition). Furthermore, a recognition memory appeared to be a permanent feature in these units. Such memory was evident in responses recorded at least 1 h after the most recent presentations of the more familiar images and may have been built up over the months of training. For these cells, the shorter-term recognition memory (seconds) and the longer-term recognition memory (hour plus) were significantly correlated (0.68). In these same cells associative memory was investigated with ten abstract images which had been randomly and permanently paired. The monkey had been taught to discriminate these five pairs from other similar pairs of images. Neither the spike count nor temporal response shape (as determined by a principal-components analysis) showed increased similarity for the images that had been paired. The cells that had both short-term and long-term recognition memory had responses to previously paired stimuli that were no more similar than expected by chance.

Anterior brain electrical asymmetries in response to reward and punishment.

A variety of recent research indicates that when subjects are induced to experience certain negative emotions, there is greater suppression of alpha power in the right than left frontal region, while during the experience of positive emotion, alpha power asymmetry in this region shows the opposite pattern. We have conceptualized this asymmetry as reflecting specialization for approach and withdrawal processes in the left and right frontal regions, respectively. In this experiment, reward and punishment contingencies were directly manipulated to produce approach and withdrawal emotional states. In addition, subjects responded to imperative stimuli using either an approach response (finger press) or a withdrawal response (finger lift). EEG was recorded from multiple scalp locations. During the foreperiod prior to the response to the imperative stimuli, the EEG was extracted, Fourier-transformed and power computed in the theta, alpha and beta frequency bands. In addition, the contingent negative variation (CNV) was derived from the identical epoch. Reward trials were associated with greater left frontal alpha power suppression than punishment trials, while during the latter trials, there was greater right-sided frontal alpha power suppression than during reward trials. There was also some evidence to indicate that withdrawal responses were associated with greater right-sided alpha power suppression in the temporo-parietal region compared with approach responses. Power in the theta and beta bands did not systematically vary with condition. The CNV was larger during trials on which subjects responded quickly compared with slow trials, but did not differentiate between reward and punishment contingencies. The findings support the hypothesis that approach-related processes can be differentiated from withdrawal-related processes on the basis of asymmetrical shifts in alpha power in the frontal region. They also indicate that the CNV and spectral power estimates from the identical epochs reflect different neural processes.

Hemispheric asymmetry in event related potentials associated with positive and negative emotions.

Event-related potentials from symmetrical points of the left and right frontal and occipital cortex were recorded while subjects experienced positive and negative emotions. The emotions were elicited by either missing or hitting a target with a photoelectric gun. Twenty three right-handers (10 males and 13 females) were tested. Each subject took part in two sessions. In the first session the subjects were informed about their performance (hit or miss) after each shot. In the second, control session, no feedback was given. The amplitudes of P180 potential registered from the occipital cortex were higher in the right than in the left cerebral hemisphere, irrespectively of subjects' performance (i.e. a miss or a hit). No such tendency was observed in potentials registered from the frontal cortex. These regularities emerged only in the feedback situation, i.e. when subjects were informed about their performance, although higher ERPs were registered for hits than for misses. The results support the hypothesis that the posterior region of the right hemisphere is more engaged than the left one in experiencing emotions, irrespectively of their sign.

Hemispheric differences in evoked potentials to faces and words.

Sixteen right-handed subjects (8 male and 8 female) were asked to compare two faces or two words successively presented at the centre of the visual field. The brain's electrical activity was recorded from the scalp at symmetrical points of the left and right occipital lobes (0(1) and 0(2)) and posterior temporal lobes (T5 and T6). The reference electrode was placed on the scalp vertex (Cz). A multi-factor analysis of variance revealed significant hemispheric differences of the N243 and P406 amplitudes. For the N243 the opposite asymmetry was found for faces and words. For the face matching the N243 amplitude was higher in the right hemisphere, whereas for word matching it was higher in the left hemisphere. For the P406 the asymmetry was in the same direction both for faces and words, with higher amplitude in the left hemisphere. In the case of face matching the hemispheric difference in the P406 was more pronounced, due to a negative shift of the potential in the left hemisphere in the latency range of 200-1,500 ms. Functional asymmetry of the brain in face perception thus appears to be reflected in the brain's electrical activity. We conclude that differentiation in hemispheric functions takes place while encoding information about stimulus in short term memory.

Cortical topography of event-related potentials to winning and losing in a video tennis game.

The event-related potentials (ERP) in frontal and posterior associative cortex in right and left hemispheres were studied in two different outcomes of a television tennis game. These outcomes were 'win' and 'loss' of the ball, the first serving as a model of positive, the second as a model of negative emotional reactions. The ERPs consisted of 4 waves: P300, N600, P800, N1000. The most characteristic interhemispheric difference for 'win' was an increase of N600 in the left posterior associative cortex, and for 'loss', a decrease of P800 in the right frontal area. Thus, the positive and negative emotional reactions have specific spatio-temporal cortical organizations. The topography of ERP related to positive and negative emotions was disturbed in depressive patients. The patients revealed a larger negativity of the right posterior associative cortex and the left frontal cortex waves both at winning and losing the ball.

[Processes of verbal memory in patients with involuntary movements treated by thalamotomy]. / Przebieg procesów pamieci slownej u chorych z ruchami mimowolnymi leczonych talamotomia.

The authors tested verbal memory and learning in 15 patients with motor disturbances treated by ventrolateral thalamotomy before operation and late after it, after a mean time of 5.8 years. Disturbances of verbal memory in the form of retrieval of information from the memory stores and disturbances of learning of verbal material were found already before the operation. In comparative investigations late after the operation greater disturbances of verbal memory were observed with disturbances of verbal retrieval from memory stores after damage to the VL nucleus in the left as well as right thalamus. On the other hand, no decrease of the mental efficiency of these patients was demonstrated.

Right hemisphere superiority in the perception of different kinds of non-verbal material.

Hemispheric asymmetries in different perceptual functions have been tested using the method of lateral presentation of stimuli i.e. in the left or right visual field. The first two experiments showed the right hemisphere advantage in the accuracy of detection of stereoscopic depth and in the strength of the tilt after-effect, i.e. in such phenomena which seem to be produced in the striate cortex. The third experiment, in which evoked potentials from point 01 and 02 during face perception were recorded, revealed the existence of right hemisphere superiority as early as 150 ms after stimulus presentation. These results indicate that the two hemispheres can already differ in their functions at the sensory level of processing.

Event-related potentials associated with positive and negative emotions.

To study the cortical regulation of emotions, event-related potentials (ERP) were recorded in the situation of a television tennis game. Winning the ball was used as a model of a positive and losing it was that of a negative emotional reaction.

Hemispheric differences in evoked potentials to pictures of faces in the left and right visual fields.

Fifteen right-handed women evaluated the similarity of two faces presented to them either in the left or in the right visual field. The subjects' task was to decide whether the faces were the same or different and accordingly to press a button or abstain from doing so. Errors made by the subjects and the visual evoked potentials (VEPs) from points O1 and O2 referred to point CZ were recorded. Behavioural and electrophysiological results demonstrated the superiority of the right hemisphere in the perception of faces. The subjects made fewer errors when faces were presented in the left visual field. The number of errors also decreased when the presented faces were different from each other. Analysis of the VEPs indicates the existence of hemispheric asymmetry as early as 100 msec after the first stimulus disappeared. The asymmetry is larger in response to the second stimulus. On the basis of these results we conclude that differentiation in hemispheric functions takes place in the phase of short-term memory. The smaller number of errors made when the presented faces were different we explain by the strategy applied by the subjects.

Visually evoked potentials to pattern stimuli in cortex of binocularly deprived cats.

Visually evoked potentials (VEPs) were compared in 7 normally reared cats (N cats) and 9 cats deprived of pattern vision during postnatal period. In 4 deprived cats (D cats) recording was done immediately after deprivation period which lasted from 6 to 24 months. In 5 cats (DE cats) 6 months of deprivation was followed by 4-18 months of visual experience. Two stimuli were used: a large stationary stimulus (a 30 per 30 degrees grating pattern illuminated by flash) and a small moving stimulus (a smaller grating pattern was located in different parts of visual field and illuminated by a moving 1 per 4 degrees light slit). The VEPs were recorded in the marginal, suprasylvian, ectosylvian and sigmoid gyri. As compared with N cats, in D cats the VEPs in all cortical areas were of simpler form, more variable and of greater amplitude. Moreover, in contrast to N cats, in D cats the VEPs were of similar amplitude when evoked from the contra or homolateral visual field. However, results in DE cats showed that these changes are largely reversible.