Neural oscillations suggest periodicity encoding during auditory beat processing in the premature brain.

When exposed to rhythmic patterns with temporal regularity, adults exhibit an inherent ability to extract and anticipate an underlying sequence of regularly spaced beats, which is internally constructed, as beats are experienced even when no events occur at beat positions (e.g., in the case of rests). Perception of rhythm and synchronization to periodicity is indispensable for development of cognitive functions, social interaction, and adaptive behavior. We evaluated neural oscillatory activity in premature newborns (n = 19, mean age, 32 ± 2.59 weeks gestational age) during exposure to an auditory rhythmic sequence, aiming to identify early traces of periodicity encoding and rhythm processing through entrainment of neural oscillations at this stage of neurodevelopment. The rhythmic sequence elicited a systematic modulation of alpha power, synchronized to expected beat locations coinciding with both tones and rests, and independent of whether the beat was preceded by tone or rest. In addition, the periodic alpha-band fluctuations reached maximal power slightly before the corresponding beat onset times. Together, our results show neural encoding of periodicity in the premature brain involving neural oscillations in the alpha range that are much faster than the beat tempo, through alignment of alpha power to the beat tempo, consistent with observations in adults on predictive processing of temporal regularities in auditory rhythms. RESEARCH HIGHLIGHTS: In response to the presented rhythmic pattern, systematic modulations of alpha power showed that the premature brain extracted the temporal regularity of the underlying beat. In contrast to evoked potentials, which are greatly reduced when there is no sounds event, the modulation of alpha power occurred for beats coinciding with both tones and rests in a predictive way. The findings provide the first evidence for the neural coding of periodicity in auditory rhythm perception before the age of term.

Negative central activity in extremely preterm newborns: EEG characterization and relationship with brain injuries and neurodevelopmental outcome.

OBJECTIVE: To characterize Negative Central Activity (NCA), an overlooked electroencephalographic activity of preterm newborns and investigate its relationship with brain injuries, dysfunction, and neurodevelopmental outcome. METHODS: 109 preterm infants (23-28 weeks) were retrospectively included. NCA were selected at the negative peak on EEG. Individual averaged NCA were automatically characterized. Brain structural data were collected from cranial ultrasounds (cUS). The neurodevelopmental outcome at two years of age was assessed by the Denver Developmental Screening Test-II. RESULTS: Thirty-six (33%) children showed NCA: 6,721 NCA were selected, a median of 75 (interquartile range, 25/157.3) per EEG. NCA showed a triphasic morphology, with a mean amplitude and duration of the negative component of 24.6-40.0 µV and 222.7-257.3 ms. The presence of NCA on EEG was associated with higher intraventricular haemorrhage (IVH) grade on the first (P = 0.016) and worst neonatal cUS (P < 0.001) and poorer neurodevelopmental outcome (P < 0.001). CONCLUSIONS: NCA is an abnormal EEG feature of extremely preterm newborns that may correspond to the functional neural impact of a vascular pathology. SIGNIFICANCE: The NCA relationships with an adverse outcome and the presence/severity of IVH argue for considering NCA in the assessment of pathological processes in the developing brain network and for early outcome prediction.

Rhythm in the Premature Neonate Brain: Very Early Processing of Auditory Beat and Meter.

The ability to extract rhythmic structure is important for the development of language, music, and social communication. Although previous studies show infants' brains entrain to the periodicities of auditory rhythms and even different metrical interpretations (e.g., groups of two vs three beats) of ambiguous rhythms, whether the premature brain tracks beat and meter frequencies has not been explored previously. We used high-resolution electroencephalography while premature infants (n = 19, 5 male; mean age, 32 ± 2.59 weeks gestational age) heard two auditory rhythms in the incubators. We observed selective enhancement of the neural response at both beat- and meter-related frequencies. Further, neural oscillations at the beat and duple (groups of 2) meter were phase aligned with the envelope of the auditory rhythmic stimuli. Comparing the relative power at beat and meter frequencies across stimuli and frequency revealed evidence for selective enhancement of duple meter. This suggests that even at this early stage of development, neural mechanisms for processing auditory rhythms beyond simple sensory coding are present. Our results add to a few previous neuroimaging studies demonstrating discriminative auditory abilities of premature neural networks. Specifically, our results demonstrate the early capacities of the immature neural circuits and networks to code both simple beat and beat grouping (i.e., hierarchical meter) regularities of auditory sequences. Considering the importance of rhythm processing for acquiring language and music, our findings indicate that even before birth, the premature brain is already learning this important aspect of the auditory world in a sophisticated and abstract way.SIGNIFICANCE STATEMENT Processing auditory rhythm is of great neurodevelopmental importance. In an electroencephalography experiment in premature newborns, we found converging evidence that when presented with auditory rhythms, the premature brain encodes multiple periodicities corresponding to beat and beat grouping (meter) frequencies, and even selectively enhances the neural response to meter compared with beat, as in human adults. We also found that the phase of low-frequency neural oscillations aligns to the envelope of the auditory rhythms and that this phenomenon becomes less precise at lower frequencies. These findings demonstrate the initial capacities of the developing brain to code auditory rhythm and the importance of special care to the auditory environment of this vulnerable population during a highly dynamic period of neural development.

The frontal sharp transient in newborns: An endogenous neurobiomarker concomitant to the physiological and critical transitional period around delivery?

The frontal sharp transient (FST) consists of transient electrical activity recorded around the transitional period from the in to ex utero environment. Although its positive predictive value is assumed, nothing is known about its functionality or origin. The objectives were (i) to define its characteristics and (ii) to develop functional hypothesis. The 128-channels high-resolution electroencephalograms of 20 healthy newborns (37.1-41.6 weeks) were studied. The morphological and time-frequency characteristics of 418 FSTs were analyzed. The source localization of the FSTs was obtained using a finite element head model (5 layers and fontanels) and various source localization methods (distributed and dipolar). The characteristics (duration, slopes, and amplitude) and the localization of FSTs were not modulated by the huge developmental neuronal processes that occur during the very last period of gestation. The sources were located beneath the ventral median part of the frontal lobe around the interhemispheric fissure, suggesting that the olfactory bulbs and orbitofrontal cortex, essential in olfaction and the mother-infant attachment relationship, are likely candidates for the generation of FSTs. FSTs may contribute to the implementation of the functionalities of brain structures involved in the higher-order processing necessary for survival ahead of delivery, with a genetic fingerprint.

Preterm neonates distinguish rhythm violation through a hierarchy of cortical processing.

Rhythm is a fundamental component of the auditory world, present even during the prenatal life. While there is evidence that some auditory capacities are already present before birth, whether and how the premature neural networks process auditory rhythm is yet not known. We investigated the neural response of premature neonates at 30-34 weeks gestational age to violations from rhythmic regularities in an auditory sequence using high-resolution electroencephalography and event-related potentials. Unpredicted rhythm violations elicited a fronto-central mismatch response, indicating that the premature neonates detected the rhythmic regularities. Next, we examined the cortical effective connectivity underlying the elicited mismatch response using dynamic causal modeling. We examined the connectivity between cortical sources using a set of 16 generative models that embedded alternate hypotheses about the role of the frontal cortex as well as backward fronto-temporal connection. Our results demonstrated that the processing of rhythm violations was not limited to the primary auditory areas, and as in the case of adults, encompassed a hierarchy of temporo-frontal cortical structures. The result also emphasized the importance of top-down (backward) projections from the frontal cortex in explaining the mismatch response. Our findings demonstrate a sophisticated cortical structure underlying predictive rhythm processing at the onset of the thalamocortical and cortico-cortical circuits, two months before term.

Evolution of cross-frequency coupling between endogenous oscillations over the temporal cortex in very premature neonates.

Temporal theta activity in coalescence with slow-wave (TTA-SW) is one of the first neurobiomarkers of the neurodevelopment of perisylvian networks in the electroencephalography (EEG). Dynamic changes in the microstructure and activity within neural networks are reflected in the EEG. Slow oscillation slope can reflect synaptic strength, and cross-frequency coupling (CFC), associated with several putative functions in adults, can reflect neural communication. Here, we investigated the evolution of CFC, in terms of SW theta phase-amplitude coupling (PAC), during the course of very early development between 25 and 32 weeks of gestational age in 23 premature neonates. We used high-resolution EEG and dipole models as spatial filters to extract the source waveforms corresponding to TTA-SW. We also carried out nonlinear phase-dependent correlation measurements to examine whether the characteristics of the SW slopes are associated with TTA-SW coupling. We show that neurodevelopment leads to temporal accumulation of the SW theta PAC toward the trough of SW. Steepness of the negative going slope of SW determined the degree of this coupling. Systematic modulation of SW-TTA CFC during development is a signature of the complex development of local cortico-cortical perisylvian networks and distant thalamo-cortical neural circuits driving this nested activity over the perisylvian networks.

Differences in behavioral and cortical indices in pianists and non-musicians during a non-musical motor planning task: An event-related potential study.

Psychological studies have shown that music has an impact on human cognitive function. We aimed to compare the performance and neural activity of pianists and non-musicians during a non-musical motor-planning task. In addition, we investigated the effect of task complexity on the characteristics of the behavioral and neural responses. The participants had to grasp a hexagonal knob with their right hand and rotate it 60° or 180° clockwise (CW) or counterclockwise (CCW). We examined the groups in terms of the amplitude of the P2 component in the event-related potential (at the neural level) and the planning time, grasping time, releasing time, and planning pattern for initial grip selection (at the behavioral level). At the behavioral level, we observed no significant difference between groups, while at the neural level; we found an interaction between direction and group indicating that pianists showed lower P2 amplitude in the CW directions. However, there was no significant difference between groups in the CCW direction. A significant main effect of rotation was revealed at both the neural and behavioral levels; increasing the rotation angle led to an increase in the planning time and the P2 amplitude, indicating a complexity effect. In conclusion, we observed that pianists had lower P2 amplitude in lateral movements than non-musicians; however, due to the lack of behavioral group differences, further research is warranted to support the far-transfer theory in this field.

The Investigation of Simultaneous EEG and Eye Tracking Characteristics During Fixation Task in Mild Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that occurs many years before the first clinical symptoms. Finding more exact, significant, and valuable criteria or indices for the diagnosis of the mild form of Alzheimer's disease is very important for clinical and research purposes. Electroencephalography (EEG) and eye tracking biomarkers would provide noninvasive tools for the early detection of AD. Due to the advantages of EEG and eye tracking, in this study, we employed them simultaneously to conduct research on the mild AD. For this purpose, 19 patients with mild AD were compared with 19 gender- and age-matched normal subjects who did not have any history of cognitive or neurological disorders. EEG and eye-tracking data were concurrently collected in both groups in a fixation task. Our results revealed that the total fixation duration was significantly shorter for the AD patients, but their fixation frequency was more than that of the controls. In addition, increased theta power and decreased alpha power were observed in the AD group. Interestingly, there was a statistically significant correlation between fixation frequency and alpha power in the parietal area in the control group. However, this connection was not statistically significant in the AD group. The findings also indicated an elevated coherence in the AD patients in the parieto-occipital area. It is assumed that the AD patients might use the neural compensational processes for the fixation state. This study provides evidence for the simultaneously EEG and eye-tracking changes in the areas, which are involved in the control of the fixational eye movements.

Back to basics: the neuronal substrates and mechanisms that underlie the electroencephalogram in premature neonates.

Electroencephalography is the only clinically available technique that can address the premature neonate normal and pathological functional development week after week. The changes in the electroencephalogram (EEG) result from gradual structural and functional modifications that arise during the last trimester of pregnancy. Here, we review the structural changes over time that underlie the establishment of functional immature neural networks, the impact of certain anatomical specificities (fontanelles, connectivity, etc.) on the EEG, limitations in EEG interpretation, and the utility of high-resolution EEG (HR-EEG) in premature newborns (a promising technique with a high degree of spatiotemporal resolution). In particular, we classify EEG features according to whether they are manifestations of endogenous generators (i.e. theta activities that coalesce with a slow wave or delta brushes) or come from a broader network. Furthermore, we review publications on EEG in premature animals because the data provide a better understanding of what is happening in premature newborns. We then discuss the results and limitations of functional connectivity analyses in premature newborns. Lastly, we report on the magnetoelectroencephalographic studies of brain activity in the fetus. A better understanding of complex interactions at various structural and functional levels during normal neurodevelopment (as assessed using electroencephalography as a benchmark method) might lead to better clinical care and monitoring for premature neonates.

The intimate relationship between coalescent generators in very premature human newborn brains: Quantifying the coupling of nested endogenous oscillations.

Temporal theta slow-wave activity (TTA-SW) in premature infants is a specific neurobiomarker of the early neurodevelopment of perisylvian networks observed as early as 24 weeks of gestational age (wGA). It is present at the turning point between non-sensory driven spontaneous networks and cortical network functioning. Despite its clinical importance, the underlying mechanisms responsible for this spontaneous nested activity and its functional role have not yet been determined. The coupling between neural oscillations at different timescales is a key feature of ongoing neural activity, the characteristics of which are determined by the network structure and dynamics. The underlying mechanisms of cross-frequency coupling (CFC) are associated with several putative functions in adults. In order to show that this generic mechanism is already in place early in the course of development, we analyzed electroencephalography recordings from sleeping preterm newborns (24-27 wGA). Employing cross-frequency phase-amplitude coupling analyses, we found that TTAs were orchestrated by the SWs defined by a precise temporal relationship. Notably, TTAs were synchronized to the SW trough, and were suppressed during the SW peak. Spontaneous endogenous TTA-SWs constitute one of the very early signatures of the developing temporal neural networks with key functions, such as language and communication. The presence of a fine-tuned relationship between the slow activity and the TTA in premature neonates emphasizes the complexity and relative maturity of the intimate mechanisms that shape the CFC, the disruption of which can have severe neurodevelopmental consequences.

Motivated forgetting increases the recall time of learnt items: Behavioral and event related potential evidence.

We investigated modulation of the recall time in a motivated forgetting (MF) paradigm and the neural manifestation of it through event related potential (ERP) analysis. We studied whether compared to failed attempts in suppression, partial success can potentiate control mechanisms and this might manifest, neurally as modulation of ERP components related to conscious recollection, and behaviorally as delayed recall of learnt items. We employed a modified version of the Think\No-Think paradigm with dominant number of No-Think words (cued to forget). We defined a forgetting index as FI = Final Recall Time-Initial Recall Time. The MF trials were separated into three conditions according to their corresponding FI; Forget, Delayed Recall, and Recall conditions. The findings revealed significant late ERP effects in terms of a late parietal positivity (LPP), modulated by the item condition, that appeared to reflect the consequence of conscious suppression on actual retrieval of stored memory. Over the same topographic location, FI was negatively correlated with the LPP amplitude, demonstrating the consequence of inhibition processing during MF in modulating the recall time. The negative correlation between LPP and FI provides evidence that increased recall time due to MF is also related to reduced activity, probably in the hippocampal-parietal network, corresponding to recollection of suppressed memories.

Detection of reaching intention using EEG signals and nonlinear dynamic system identification.

BACKGROUND AND OBJECTIVES: Low frequency electroencephalography (EEG) signals are associated with preparation of movement and thus provide valuable information for brain-machine interface applications. The purpose of this study was to detect movement intention from EEG signals before execution of self-paced arm reaching movements. METHODS: Ten healthy individuals were recruited. Movement onset was determined from surface electromyography recordings time-locked with EEG signals. Unlike previous studies, which employed feature extraction and classification for decoding, a nonlinear dynamic multiple-input/single output (MISO) model was developed. The MISO model consisted of a cascade of Volterra structures and a threshold block, generating the binary output corresponding to intention/no-intention. The modeling process included input selection from a pool of different EEG channels. The predictive performance of the model was evaluated using the receiver operating characteristics curve, from which the optimum threshold was also selected. The Mann-Whitney statistics was employed to select the significant EEG channels for the output by examining the statistical significance of improvement in the predictive capability of the model when the respective channels were included. RESULTS: With the proposed approach, movement intention was detected approximately 500 ms before the movement onset and on average, with an accuracy of 96.37 ± 0.94%, a sensitivity of 77.93 ± 4.40% and a specificity of 98.52 ± 1.19%. CONCLUSIONS: The model output can be converted to motion commands for neuroprosthetic devices and exoskeletons in future applications.

Opposite effect of motivated forgetting on sleep spindles during stage 2 and slow wave sleep.

Memories selectively benefit from sleep. In addition to the importance of the consolidation of relevant memories, the capacity to forget unwanted memories is also crucial. We investigated the effect of suppressing unwanted memories on electroencephalography activity of subsequent sleep using a motivated forgetting (MF) paradigm as compared with a control non-forgetting task. Subjects were randomly assigned to nap or no-nap groups. We used a modified version of the think/no-think paradigm with dominant number of no-think words cued to be forgotten and included only subjects capable of suppressing unwanted memories by performing an initial subject inclusion experiment. In both groups and conditions, the performance of the subjects in recalling the word pairs learned in the beginning of the day was evaluated in a final recall test. We found that both nap and no-nap groups recalled significantly less no-think words in the MF condition compared to the control condition. Moreover, for the nap group, in the MF compared to the control condition, spindle power and density increased during stage 2 (S2) whereas they decreased during slow wave sleep (SWS). Interestingly, recall performance of no-think words was negatively correlated with spindle power during S2 whereas it was positively correlated with spindle power during SWS. These results indicate that sleep spindles are sensitive to the previous MF experiences and suggest a differential role of sleep spindles during S2 and SWS in memory processing during sleep.

Lost in music: Neural signature of pleasure and its role in modulating attentional resources.

We investigated the neural correlates of pleasure induced by listening to highly pleasant and neutral musical excerpts using electroencephalography (EEG). Power spectrum analysis of EEG data showed a distinct gradual change in the power of low-frequency oscillations in response to highly pleasant, but not neutral, musical excerpts. Specifically, listening to highly pleasant music was associated with (i) relatively higher oscillatory activity in the theta band over the frontocentral (FC) area and in the alpha band over the parieto-occipital area, and (ii) a gradual increase in the oscillatory power over time. Correlation analysis between behavioral and electrophysiological data revealed that theta power over the FC electrodes was correlated with subjective assessment of pleasantness while listening to music. To study the link between attention and positive valence in our experiments, volunteers performed a delayed match-to-sample memory task while listening to the musical excerpts. The subjects' performances were significantly lower under highly pleasant conditions compared to neutral conditions. Listening to pleasant music requires higher degrees of attention, leading to the observed decline in memory performance. Gradual development of low-frequency oscillations in the frontal and posterior areas may be at least partly due to gradual recruitment of higher levels of attention over time in response to pleasurable music.

Slow spindles are associated with cortical high frequency activity.

Thalamocortical network shows self-sustained oscillations in a broad frequency range especially during slow wave sleep when cortical neurons show synchronized transitions between a quiescent down state and an active up state with beta and gamma oscillations. Inconsistent with previous models, thalamocortical spindles are separated into slow spindles (8_12 Hz) and fast spindles (13_17 Hz) with differential properties. We proposed that cortical high frequency (∼ 25 Hz) activity during up states is the key ingredient for the generation of slow spindles. In fact, the nonlinear interaction between cortical high frequency and thalamic oscillations at fast spindle frequency reproduces oscillations in the range of the difference between the two frequencies that lies into the range of slow spindle. The developed simple deterministic thalamocortical model is able to reproduce up and down states with stochastic high-frequency up-state activity as well as both fast and slow spindles. In agreement with the previous experimental observations, the fast and slow spindles are generated at opposing phases of the up state. To further confirm the causal relationship between slow spindles and cortical high frequency oscillations, we next showed that externally applied high frequency stimulation enhanced the slow spindle activity. Moreover, the prediction of the model was validated experimentally by recording EEG from subjects during nap. Both model and experimental results show increase in high frequency activity before slow spindles. Our findings suggest the important role of cortical high frequency activity in the generation of slow spindles.

Culture Modulates the Brain Response to Harmonic Violations: An EEG Study on Hierarchical Syntactic Structure in Music.

We investigated the role of culture in processing hierarchical syntactic structures in music. We examined whether violation of non-local dependencies manifest in event related potentials (ERP) for Western and Iranian excerpts by recording EEG while participants passively listened to sequences of modified/original excerpts. We also investigated oscillatory and synchronization properties of brain responses during processing of hierarchical structures. For the Western excerpt, subjective ratings of conclusiveness were marginally significant and the difference in the ERP components fell short of significance. However, ERP and behavioral results showed that while listening to culturally familiar music, subjects comprehended whether or not the hierarchical syntactic structure was fulfilled. Irregularities in the hierarchical structures of the Iranian excerpt elicited an early negativity in the central regions bilaterally, followed by two later negativities from 450-700 to 750-950 ms. The latter manifested throughout the scalp. Moreover, violations of hierarchical structure in the Iranian excerpt were associated with (i) an early decrease in the long range alpha phase synchronization, (ii) an early increase in the oscillatory activity in the beta band over the central areas, and (iii) a late decrease in the theta band phase synchrony between left anterior and right posterior regions. Results suggest that rhythmic structures and melodic fragments, representative of Iranian music, created a familiar context in which recognition of complex non-local syntactic structures was feasible for Iranian listeners. Processing of neural responses to the Iranian excerpt indicated neural mechanisms for processing of hierarchical syntactic structures in music at different levels of cortical integration.

Towards an SEMG-based tele-operated robot for masticatory rehabilitation.

This paper proposes a real-time trajectory generation for a masticatory rehabilitation robot based on surface electromyography (SEMG) signals. We used two Gough-Stewart robots. The first robot was used as a rehabilitation robot while the second robot was developed to model the human jaw system. The legs of the rehabilitation robot were controlled by the SEMG signals of a tele-operator to reproduce the masticatory motion in the human jaw, supposedly mounted on the moving platform, through predicting the location of a reference point. Actual jaw motions and the SEMG signals from the masticatory muscles were recorded and used as output and input, respectively. Three different methods, namely time-delayed neural networks, time delayed fast orthogonal search, and time-delayed Laguerre expansion technique, were employed and compared to predict the kinematic parameters. The optimal model structures as well as the input delays were obtained for each model and each subject through a genetic algorithm. Equations of motion were obtained by the virtual work method. Fuzzy method was employed to develop a fuzzy impedance controller. Moreover, a jaw model was developed to demonstrate the time-varying behavior of the muscle lengths during the rehabilitation process. The three modeling methods were capable of providing reasonably accurate estimations of the kinematic parameters, although the accuracy and training/validation speed of time-delayed fast orthogonal search were higher than those of the other two aforementioned methods. Also, during a simulation study, the fuzzy impedance scheme proved successful in controlling the moving platform for the accurate navigation of the reference point in the desired trajectory. SEMG has been widely used as a control command for prostheses and exoskeleton robots. However, in the current study by employing the proposed rehabilitation robot the complete continuous profile of the clenching motion was reproduced in the sagittal plane.

In vitro investigation of heat transfer phenomenon in human immature teeth.

Background and aims. Heat generated within tooth during clinical dentistry can cause thermally induced damage to hard and soft components of the tooth (enamel, dentin and pulp). Geometrical characteristics of immature teeth are different from those of mature teeth. The purpose of this experimental and theoretical study was to investigate thermal changes in immature permanent teeth during the use of LED light-curing units (LCU). Materials and methods. This study was performed on the second mandibular premolars. This experimental investiga-tion was carried out for recording temperature variations of different sites of tooth and two dimensional finite element models were used for heat transfer phenomenon in immature teeth. Sensitivity analysis and local tests were included in the model validation phase. Results. Overall, thermal stimulation for 30 seconds with a low-intensity LED LCU increased the temperature from 28°C to 38°C in IIT (intact immature tooth) and PIT (cavity-prepared immature tooth). When a high-intensity LED LCU was used, tooth temperature increased from 28°C to 48°C. The results of the experimental tests and mathematical modeling illustrated that using LED LCU on immature teeth did not have any detrimental effect on the pulp temperature. Conclusion. Using LED LCU in immature teeth had no effect on pulp temperature in this study. Sensitivity analysis showed that variations of heat conductivity might affect heat transfer in immature teeth; therefore, further studies are required to determine thermal conductivity of immature teeth.

Automatic evaluation of pressure sore status by combining information obtained from high-frequency ultrasound and digital photography.

In this study, the different phases of pressure sore generation and healing are investigated through a combined analysis of high-frequency ultrasound (20 MHz) images and digital color photographs. Pressure sores were artificially induced in guinea pigs, and the injured regions were monitored for 21 days (data were obtained on days 3, 7, 14, and 21). Several statistical features of the images were extracted, relating to both the altering pattern of tissue and its superficial appearance. The features were grouped into five independent categories, and each category was used to train a neural network whose outputs were the four days. The outputs of the five classifiers were then fused using a fuzzy integral to provide the final decision. We demonstrate that the suggested method provides a better decision regarding tissue status than using either imaging technique separately. This new approach may be a viable tool for detecting the phases of pressure sore generation and healing in clinical settings.

Quantitative assessment of pressure sore generation and healing through numerical analysis of high-frequency ultrasound images.

Abstract-This article focuses on the development of a method to quantitatively assess the healing process of artificially induced pressure sores using high-frequency (20 MHz) ultrasound images. We induced sores in guinea pigs and monitored predefined regions on days 3, 7, 14, and 21 after sore generation. We extracted relevant parameters regarding the tissue echographic structure and attenuation properties. We examined tissue healing by defining a healing function that used the extracted parameters. We verified the significance of the extracted features by using analysis of variance and multiple comparison tests. The features displayed ascending/descending behavior during wound generation and reverse behavior during healing. We optimized the parameters of our healing function by using a pattern search method. We tested the efficiency of the optimized values by calculating the healing function value on assessment days and then comparing these results with the expected pattern of changes in the tissue conditions after removing the applied pressure. The results of this study suggest that the methodology developed may be a viable tool for quantitative assessment of pressure sores during their early generation as well as during healing stages.