Comparing the cognitive functioning of middle-aged and older foreign-origin population in Estonia to host and origin populations.

Background: In migration and health research, the healthy migrant effect has been a common finding, but it usually pertains to specific contexts only. Existing findings are inconsistent and inconclusive regarding the cognitive functioning of the (aging) foreign-origin population relative to the populations of their host and sending countries. Moreover, this comparison is an understudied design setting. Objective: We analyze the outcomes and associations of cognitive functioning outcomes of the non-institutionalized middle-aged and older population, comparing the Russian-origin population in Estonia with Estonians in Estonia and Russians in Russia in a cross-sectional design. We aim to estimate the (long-term) effects of migration on cognitive functioning in later life, contextualizing the findings in previous research on the healthy migrant effect. Data and methods: We use data from face-to-face interviews conducted within the SHARE Estonia (2010-2011) and SAGE Russia (2007-2010) surveys. Respondents aged 50+ living in urban areas were grouped by self-identified ethnicity, including 2,365 Estonians, 1,373 Russians in Estonia, and 2,339 Russians in Russia (total N = 6,077). Cognitive functioning was measured using a 25-percentile cut-off threshold for the results of two cognition outcomes - immediate recall and verbal fluency - and the odds of impairment were estimated using binary logistic regression. Results: Russian men and women living in Estonia have significantly higher odds of impairment in immediate recall than Estonian men and women, though they do not differ from Russians in Russia in the final adjusted models. The differences between all groups are non-significant if age at migration is considered. There are no significant differences between the groups in verbal fluency. Conclusion: Contrary to the commonly found healthy migrant effect, the middle-aged and older foreign-origin population in Estonia fares initially worse than the native population in the immediate recall outcome, but does not differ from their sending country population, possibly due to Russia's higher mortality rate and therefore the selective survival of healthier people. Different results depending on the cognitive functioning outcome suggest that migration may affect temporary memory more than crystallized knowledge. However, there are no differences between the groups if defined based on age at migration, which suggests that the age profile differences explain most of the groups' differences in cognitive functioning.

The association of osteoporosis and geriatric syndromes in the elderly: data from the Russian epidemiological study EVKALIPT.

Osteoporosis is associated with almost all geriatric syndromes (GSs), and the occurrence of osteoporosis in patients over 65 years of age increases by 1.2-2.5 times. Early diagnosis of osteoporosis and GSs is very important. Additional programs should be adopted by the state to introduce information about the possibilities of working with elderly patients. PURPOSE: To analyze associations of osteoporosis with geriatric syndromes in patients aged 65 years and older in the Russian Federation. METHODS: A total of 4308 patients (30% men) aged 65-107 years were examined and distributed into 3 age groups (65-74 years, 75-84 years, and 85 years and older). All patients underwent a comprehensive geriatric assessment. In the "Falls and risk of falls" module, the number and circumstances of falls over the previous year were analyzed, as well as the history of fractures. The presence of osteoporosis was determined based on medical records. Physical examination included anthropometric measurements and standard enquiry, short physical performance battery (SPPB), dynamometry, measurement of gait velocity, Mini-Cog test, and orthostatic test. RESULTS: A total of 507 patients (11.8%) had evidence of osteoporosis; indications of low-energy fractures in history were recorded in 739 (17.3%) patients. Patients with osteoporosis were older, shorter, and predominantly women; had a lower body weight and a higher Charlson comorbidity index; and took more drugs. Patients with osteoporosis had lower gait velocity, hand grip strength, Barthel index value, and scores of the Lawton instrumental activities of daily living scale, the MNA (Mini Nutritional Assessment) short-form, and the SPPB. Osteoporosis is associated with almost all geriatric syndromes (GSs), and the occurrence of osteoporosis in patients over 65 years of age increases by 1.2-2.5 times. CONCLUSIONS: Osteoporosis is associated with almost all GSs. The association of osteoporosis with advanced GSs aggravates the condition of these patients. Early diagnosis of osteoporosis and GSs is very important. Additional programs should be adopted by the state to introduce information about the possibilities of working with elderly patients: early detection and correction of osteoporosis.

Conductivity, its anisotropy and changes as a manifestation of the features of the atomic and real structures of superprotonic [K1-x(NH4)x]3H(SO4)2 crystals.

Single crystals of [K1-x(NH4)x]3H(SO4)2 (x ≥ 0.57) grown in the K3H(SO4)2-(NH4)3H(SO4)2-H2O water-salt system are studied. The atomic structure including H atoms was determined at room temperature using X-ray structural analysis. [K1-x(NH4)x]3H(SO4)2 (x ≥ 0.57) crystals have trigonal symmetry and disordered hydrogen-bond networks at ambient conditions similar to the high-temperature phases of K3H(SO4)2, (NH4)3H(SO4)2 and other superprotonic compounds M3H(AO4)2. Impedance measurements performed on single crystals show high values of conductivity characteristic for superprotonic phases. Using the methods of impedance spectroscopy and atomic force microscopy, a significant anisotropy of the conductivity of crystals has been detected. It was also shown that there is a qualitative correlation of bulk and local conductivity measured for samples of the same composition and orientation at room temperature, which is due to the peculiarities of their crystal structure.

Crystal structure, hydrogen bonds and thermal transformations of superprotonic conductor Cs6(SO4)3(H3PO4)4.

Crystals of Cs6(SO4)3(H3PO4)4 belong to the family of alkali metal acid salts that show a high protonic conductivity at relatively low temperatures. Such properties make superprotonic crystals an excellent choice for the study of the influence of the hydrogen subsystem on the physicochemical properties and promising materials for energy-efficient technologies. Single crystals of Cs6(SO4)3(H3PO4)4 were studied by neutron diffraction methods, optical polarization microscopy, scanning electron microscopy and energy-dispersive X-ray spectroscopy. Neutron diffraction studies made it possible to determine the positions of all the atoms with high accuracy, including the H atom on a hydrogen bond characterized by a single-minimum potential, to confirm the chemical composition of the Cs6(SO4)3(H3PO4)4 crystals and their cubic symmetry in low- and high-temperature phases, and to draw conclusions about the three-dimensional system of hydrogen bonds, which is fundamentally different in comparison with other superprotonic compounds. Based on the experimental data obtained, crystal transformations with temperature changes are reported, and the stability of the chemical composition is shown.

Comparison of Pupil Dilation Responses to Unexpected Sounds in Monkeys and Humans.

Pupil dilation in response to unexpected stimuli has been well documented in human as well as in non-human primates; however, this phenomenon has not been systematically compared between the species. This analogy is also crucial for the role of non-human primates as an animal model to investigate neural mechanisms underlying the processing of unexpected stimuli and their evoked pupil dilation response. To assess this qualitatively, we used an auditory oddball paradigm in which we presented subjects a sequence of the same sounds followed by occasional deviants while we measured their evoked pupil dilation response (PDR). We used deviants (a frequency deviant, a pink noise burst, a monkey vocalization and a whistle sound) which differed in the spectral composition and in their ability to induce arousal from the standard. Most deviants elicited a significant pupil dilation in both species with decreased peak latency and increased peak amplitude in monkeys compared to humans. A temporal Principal Component Analysis (PCA) revealed two components underlying the PDRs in both species. The early component is likely associated to the parasympathetic nervous system and the late component to the sympathetic nervous system, respectively. Taken together, the present study demonstrates a qualitative similarity between PDRs to unexpected auditory stimuli in macaque and human subjects suggesting that macaques can be a suitable model for investigating the neuronal bases of pupil dilation. However, the quantitative differences in PDRs between species need to be investigated in further comparative studies.

Representation of Auditory Task Components and of Their Relationships in Primate Auditory Cortex.

The current study aimed to resolve some of the inconsistencies in the literature on which mental processes affect auditory cortical activity. To this end, we studied auditory cortical firing in four monkeys with different experience while they were involved in six conditions with different arrangements of the task components sound, motor action, and water reward. Firing rates changed most strongly when a sound-only condition was compared to a condition in which sound was paired with water. Additional smaller changes occurred in more complex conditions in which the monkeys received water for motor actions before or after sounds. Our findings suggest that auditory cortex is most strongly modulated by the subjects' level of arousal, thus by a psychological concept related to motor activity triggered by reinforcers and to readiness for operant behavior. Our findings also suggest that auditory cortex is involved in associative and emotional functions, but not in agency and cognitive effort.

Basal cell carcinoma invasion depth determined with 30 and 75 MHz high-frequency ultrasound and histopathology - a comparative study.

AIM: To compare the depth spread of basal cell carcinoma (BCC) measured by histological examination and high-frequency ultrasound (HFUS) imaging with 30-MHz and 75-MHz probes. MATERIALS AND METHODS: HFUS skin imaging was used to examine 27 BCCs. A specialized high-resolution digital ultrasound imaging system DUB (TPM GmbH, Germany) with 75-MHz and 30-MHz probes was used. After HFUS scanning, the BCCs biopsy samples were collected by punch biopsy or surgical excision for the morphological examination. Based on the histomorphology results obtained, the tumors were divided into thin (≤1 mm invasion depth) and thick (>1 mm invasion depth). Each BCC spread depth was measured during the HFUS examination with 75-MHz and 30-MHz ultrasound probes and morphological examination. RESULTS: Thin BCCs average invasiondepth measured histologically was 0.494±0.212 mm. Its average depth obtained with HFU examination with 75-MHz and 30-MHz probes was 0.591±0.265 and 0.734±0.123 mm, respectively. High, statistically significant correlation betweenthe histological and 75 MHz HFU measurements was obtained (r=0.870). The correlation was weak (r=0.290) when using a 30 MHz transducer. The average thick BCC invasion depth values obtained with the histological examination and 30 MHz HFUS scanning was 1.845±0.718 mm and 1.995±0.699 mm, respectively. High, statistically significant (r=0.951) correlation between the thick BCC spread depth measured with 30 MHz transducer and histomorphological examination was obtained. CONCLUSIONS: In cases of BCCs with thickness of ≤1 mm, there was a high correlation (r=0.870) of the tumor spread depth between micromorphological measurements and the results obtained using a 75 MHz transducer and in cases of BCCs with thickness of >1 mm, a very high correlation (r=0.951) of the tumor spread depth was observed between histomorphometry and30 MHz transducer measurements.

Predictive cues for auditory stream formation in humans and monkeys.

Auditory perception is improved when stimuli are predictable, and this effect is evident in a modulation of the activity of neurons in the auditory cortex as shown previously. Human listeners can better predict the presence of duration deviants embedded in stimulus streams with fixed interonset interval (isochrony) and repeated duration pattern (regularity), and neurons in the auditory cortex of macaque monkeys have stronger sustained responses in the 60-140 ms post-stimulus time window under these conditions. Subsequently, the question has arisen whether isochrony or regularity in the sensory input contributed to the enhancement of the neuronal and behavioural responses. Therefore, we varied the two factors isochrony and regularity independently and measured the ability of human subjects to detect deviants embedded in these sequences as well as measuring the responses of neurons the primary auditory cortex of macaque monkeys during presentations of the sequences. The performance of humans in detecting deviants was significantly increased by regularity. Isochrony enhanced detection only in the presence of the regularity cue. In monkeys, regularity increased the sustained component of neuronal tone responses in auditory cortex while isochrony had no consistent effect. Although both regularity and isochrony can be considered as parameters that would make a sequence of sounds more predictable, our results from the human and monkey experiments converge in that regularity has a greater influence on behavioural performance and neuronal responses.

Ultrasonographic features of superficial and nodular basal cell carcinoma.

AIM: To describe the ultrasonographic findings of surface and nodular basal cell skin cancer (BCC) using high frequency ultrasonography. MATERIALS AND METHODS: We examined 60 primary BCCs in different locations with the High Frequency Ultrasound (HFU) system DUB Skin Scanner using 75 MHz and 30 MHz probes. Epidermis, dermis, and depth of tumors spread in the region of interest (ROI) were measured. Visually unchanged, contralateral skin areas were examined as the control. Results: The surface BCC most often had elongated contours, clear margins and hypoechoic structure, while the nodular BCC had round or oval outlines and diffusely hypo-heterogeneous structure with clear margins. Sclerodermiform BCCs were visualized as hypoechoic areas of irregular shape penetrating in the dermis, with wavy fuzzy margins. The average thickness of the surface BCC in the US examination was 556.28±136.95 µ, the nodular BCC thickness was 2439.71±865.92 µ and the sclerodermiform thickness was 1500±325.33 µ. A statistically significant increase in the average thickness of tumors of the nodularand scleroderma forms was observed in comparison with the surface clinical variant (p<0.05). Hyperechoic inclusions were observed in 11% of the surface BCC's and in the 100% of the nodular BCC's. Their average number was 2±0.57 and 4±4.8, with the average area of 0.03±0.02 mm2 and 0.04±0.03 mm2 (p>0.05), respectively. In the surface BCC, they were mainly located along the periphery of the hypoechoic zones. In nodular BCC, the inclusions had a peripheral and combined (center and peripheral) distribution. CONCLUSIONS: Ultrasound allows differentiating BCC as diffuse-heterogeneous, hypoechoic, formations in the dermis with distinct contours. Depending on the clinical picture, they differ in form, depth of bedding, as well as in the quantitative ratio and distribution of the point hyperechoic structures in them.

Neuronal correlates of auditory streaming in the auditory cortex of behaving monkeys.

This study tested the hypothesis that spiking activity in the primary auditory cortex of monkeys is related to auditory stream formation. Evidence for this hypothesis was previously obtained in animals that were passively exposed to stimuli and in which differences in the streaming percept were confounded with differences between the stimuli. In this study, monkeys performed an operant task on sequences that were composed of light flashes and tones. The tones alternated between a high and a low frequency and could be perceived either as one auditory stream or two auditory streams. The flashes promoted either a one-stream percept or a two-stream percept. Comparison of different types of sequences revealed that the neuronal responses to the alternating tones were more similar when the flashes promoted auditory stream integration, and were more dissimilar when the flashes promoted auditory stream segregation. Thus our findings show that the spiking activity in the monkey primary auditory cortex is related to auditory stream formation.

Neuronal Correlates of Auditory Streaming in Monkey Auditory Cortex for Tone Sequences without Spectral Differences.

This study finds a neuronal correlate of auditory perceptual streaming in the primary auditory cortex for sequences of tone complexes that have the same amplitude spectrum but a different phase spectrum. Our finding is based on microelectrode recordings of multiunit activity from 270 cortical sites in three awake macaque monkeys. The monkeys were presented with repeated sequences of a tone triplet that consisted of an A tone, a B tone, another A tone and then a pause. The A and B tones were composed of unresolved harmonics formed by adding the harmonics in cosine phase, in alternating phase, or in random phase. A previous psychophysical study on humans revealed that when the A and B tones are similar, humans integrate them into a single auditory stream; when the A and B tones are dissimilar, humans segregate them into separate auditory streams. We found that the similarity of neuronal rate responses to the triplets was highest when all A and B tones had cosine phase. Similarity was intermediate when the A tones had cosine phase and the B tones had alternating phase. Similarity was lowest when the A tones had cosine phase and the B tones had random phase. The present study corroborates and extends previous reports, showing similar correspondences between neuronal activity in the primary auditory cortex and auditory streaming of sound sequences. It also is consistent with Fishman's population separation model of auditory streaming.

Category-specific neuronal activity in left and right auditory cortex and in medial geniculate body of monkeys.

We address the question of whether the auditory cortex of the left and right hemisphere and the auditory thalamus are differently involved in the performance of cognitive tasks. To understand these differences on the level of single neurons we compared neuronal firing in the primary and posterior auditory cortex of the two hemispheres and in the medial geniculate body in monkeys while subjects categorized pitch relationships in tone sequences. In contrast to earlier findings in imaging studies performed on humans, we found little difference between the three brain regions in terms of the category-specificity of their neuronal responses, of tonic firing related to task components, and of decision-related firing. The differences between the results in humans and monkeys may result from the type of neuronal activity considered and how it was analyzed, from the auditory cortical fields studied, or from fundamental differences between these species.

Neuronal activity in primate auditory cortex during the performance of audiovisual tasks.

This study aimed at a deeper understanding of which cognitive and motivational aspects of tasks affect auditory cortical activity. To this end we trained two macaque monkeys to perform two different tasks on the same audiovisual stimulus and to do this with two different sizes of water rewards. The monkeys had to touch a bar after a tone had been turned on together with an LED, and to hold the bar until either the tone (auditory task) or the LED (visual task) was turned off. In 399 multiunits recorded from core fields of auditory cortex we confirmed that during task engagement neurons responded to auditory and non-auditory stimuli that were task-relevant, such as light and water. We also confirmed that firing rates slowly increased or decreased for several seconds during various phases of the tasks. Responses to non-auditory stimuli and slow firing changes were observed during both the auditory and the visual task, with some differences between them. There was also a weak task-dependent modulation of the responses to auditory stimuli. In contrast to these cognitive aspects, motivational aspects of the tasks were not reflected in the firing, except during delivery of the water reward. In conclusion, the present study supports our previous proposal that there are two response types in the auditory cortex that represent the timing and the type of auditory and non-auditory elements of a auditory tasks as well the association between elements.

Rhythm sensitivity in macaque monkeys.

This study provides evidence that monkeys are rhythm sensitive. We composed isochronous tone sequences consisting of repeating triplets of two short tones and one long tone which humans perceive as repeating triplets of two weak and one strong beat. This regular sequence was compared to an irregular sequence with the same number of randomly arranged short and long tones with no such beat structure. To search for indication of rhythm sensitivity we employed an oddball paradigm in which occasional duration deviants were introduced in the sequences. In a pilot study on humans we showed that subjects more easily detected these deviants when they occurred in a regular sequence. In the monkeys we searched for spontaneous behaviors the animals executed concomitant with the deviants. We found that monkeys more frequently exhibited changes of gaze and facial expressions to the deviants when they occurred in the regular sequence compared to the irregular sequence. In addition we recorded neuronal firing and local field potentials from 175 sites of the primary auditory cortex during sequence presentation. We found that both types of neuronal signals differentiated regular from irregular sequences. Both signals were stronger in regular sequences and occurred after the onset of the long tones, i.e., at the position of the strong beat. Local field potential responses were also significantly larger for the durational deviants in regular sequences, yet in a later time window. We speculate that these temporal pattern-selective mechanisms with a focus on strong beats and their deviants underlie the perception of rhythm in the chosen sequences.

Reaction times reflect subjective auditory perception of tone sequences in macaque monkeys.

Perceptually ambiguous stimuli are useful for testing psychological and neuronal models of perceptual organization, e.g. for studying brain processes that underlie sequential segregation and integration. This is because the same stimuli may give rise to different subjective experiences. For humans, a tone sequence that alternates between a low-frequency and a high-frequency tone is perceptually bistable, and can be perceived as one or two streams. In the current study we present a new method based on response times (RTs) which allows identification ambiguous and unambiguous stimuli for subjects who cannot verbally report their subjective experience. We required two macaque monkeys (macaca fascicularis) to detect the termination of a sequence of light flashes which were either presented alone, or synchronized in different ways with a sequence of alternating low and high tones. We found that the monkeys responded faster to the termination of the flash sequence when the tone sequence terminated shortly before the flash sequence and thus predicted the termination of the flash sequence. This RT gain depended on the frequency separation of the tones. RT gains were largest when the frequency separation was small and the tones were presumably heard mainly as one stream. RT gains were smallest when the frequency separation was large and the tones were presumably mainly heard as two streams. RT gain was of intermediate size for intermediate frequency separations. Similar results were obtained from human subjects. We conclude that the observed RT gains reflect the perceptual organization of the tone sequence, and that tone sequences with an intermediate frequency separation, as for humans, are perceptually ambiguous for monkeys.

Representation of reward feedback in primate auditory cortex.

It is well established that auditory cortex is plastic on different time scales and that this plasticity is driven by the reinforcement that is used to motivate subjects to learn or to perform an auditory task. Motivated by these findings, we study in detail properties of neuronal firing in auditory cortex that is related to reward feedback. We recorded from the auditory cortex of two monkeys while they were performing an auditory categorization task. Monkeys listened to a sequence of tones and had to signal when the frequency of adjacent tones stepped in downward direction, irrespective of the tone frequency and step size. Correct identifications were rewarded with either a large or a small amount of water. The size of reward depended on the monkeys' performance in the previous trial: it was large after a correct trial and small after an incorrect trial. The rewards served to maintain task performance. During task performance we found three successive periods of neuronal firing in auditory cortex that reflected (1) the reward expectancy for each trial, (2) the reward-size received, and (3) the mismatch between the expected and delivered reward. These results, together with control experiments suggest that auditory cortex receives reward feedback that could be used to adapt auditory cortex to task requirements. Additionally, the results presented here extend previous observations of non-auditory roles of auditory cortex and shows that auditory cortex is even more cognitively influenced than lately recognized.

Behavioral semantics of learning and crossmodal processing in auditory cortex: the semantic processor concept.

Two phenomena of auditory cortex activity have recently attracted attention, namely that the primary field can show different types of learning-related changes of sound representation and that during learning even this early auditory cortex is under strong multimodal influence. Based on neuronal recordings in animal auditory cortex during instrumental tasks, in this review we put forward the hypothesis that these two phenomena serve to derive the task-specific meaning of sounds by associative learning. To understand the implications of this tenet, it is helpful to realize how a behavioral meaning is usually derived for novel environmental sounds. For this purpose, associations with other sensory, e.g. visual, information are mandatory to develop a connection between a sound and its behaviorally relevant cause and/or the context of sound occurrence. This makes it plausible that in instrumental tasks various non-auditory sensory and procedural contingencies of sound generation become co-represented by neuronal firing in auditory cortex. Information related to reward or to avoidance of discomfort during task learning, that is essentially non-auditory, is also co-represented. The reinforcement influence points to the dopaminergic internal reward system, the local role of which for memory consolidation in auditory cortex is well-established. Thus, during a trial of task performance, the neuronal responses to the sounds are embedded in a sequence of representations of such non-auditory information. The embedded auditory responses show task-related modulations of auditory responses falling into types that correspond to three basic logical classifications that may be performed with a perceptual item, i.e. from simple detection to discrimination, and categorization. This hierarchy of classifications determine the semantic "same-different" relationships among sounds. Different cognitive classifications appear to be a consequence of learning task and lead to a recruitment of different excitatory and inhibitory mechanisms and to distinct spatiotemporal metrics of map activation to represent a sound. The described non-auditory firing and modulations of auditory responses suggest that auditory cortex, by collecting all necessary information, functions as a "semantic processor" deducing the task-specific meaning of sounds by learning.

Formation of associations in auditory cortex by slow changes of tonic firing.

We review event-related slow firing changes in the auditory cortex and related brain structures. Two types of changes can be distinguished, namely increases and decreases of firing, lasting in the order of seconds. Triggering events can be auditory stimuli, reinforcers, and behavioral responses. Slow firing changes terminate with reinforcers and possibly with auditory stimuli and behavioral responses. A necessary condition for the emergence of slow firing changes seems to be that subjects have learnt that consecutive sensory or behavioral events are contingent on reinforcement. They disappear when the contingencies are no longer present. Slow firing changes in auditory cortex bear similarities with slow changes of neuronal activity that have been observed in subcortical parts of the auditory system and in other non-sensory brain structures. We propose that slow firing changes in auditory cortex provide a neuronal mechanism for anticipating, memorizing, and associating events that are related to hearing and of behavioral relevance. This may complement the representation of the timing and types of auditory and auditory-related events which may be provided by phasic responses in auditory cortex. The presence of slow firing changes indicates that many more auditory-related aspects of a behavioral procedure are reflected in the neuronal activity of auditory cortex than previously assumed.

A multilevel and cross-modal approach towards neuronal mechanisms of auditory streaming.

We report first results of a multilevel, cross-modal study on the neuronal mechanisms underlying auditory sequential streaming, with the focus on the impact of visual sequences on perceptually ambiguous tone sequences which can either be perceived as two separate streams or one alternating stream. We combined two psychophysical experiments performed on humans and monkeys with two human brain imaging experiments which allow to obtain complementary information on brain activation with high spatial (fMRI) and high temporal (MEG) resolution. The same acoustic paradigm based on the pairing of tone sequences with visual stimuli was used in all human studies and, in an adapted version, in the psychophysical study on monkeys. Our multilevel approach provides experimental evidence that the pairing of auditory and visual stimuli can reliably introduce a bias towards either an integrated or a segregated perception of ambiguous sequences. Thus, comparable to an explicit instruction, this approach can be used to control the subject's perceptual organization of an ambiguous sound sequence without the need for the subject to directly report it. This finding is of particular importance for animal studies because it allows to compare electrophysiological responses of auditory cortex neurons to the same acoustic stimulus sequence eliciting either a segregated or integrated percept.