Time Course Of Normalization Research Articles

Integral perception, but separate processing: The perceptual normalization of lexical tones and vowels

In tonal languages, speech variability arises in both lexical tone (i.e., suprasegmentally) and vowel quality (segmentally). Listeners can use surrounding speech context to overcome variability in both speech cues, a process known as extrinsic normalization. Although vowels are the main carriers of tones, it is still unknown whether the combined percept (lexical tone and vowel quality) is normalized integrally or in partly separate processes. Here we used electroencephalography (EEG) to investigate the time course of lexical tone normalization and vowel normalization to answer this question. Cantonese adults listened to synthesized three-syllable stimuli in which the identity of a target syllable — ambiguous between high vs. mid-tone (Tone condition) or between /o/ vs. /u/ (Vowel condition) — was dependent on either the tone range (Tone condition) or the formant range (Vowel condition) of the first two syllables. It was observed that the ambiguous tone was more often interpreted as a high-level tone when the context had a relatively low pitch than when it had a high pitch (Tone condition). Similarly, the ambiguous vowel was more often interpreted as /o/ when the context had a relatively low formant range than when it had a relatively high formant range (Vowel condition). These findings show the typical pattern of extrinsic tone and vowel normalization. Importantly, the EEG results of participants showing the contrastive normalization effect demonstrated that the effects of vowel normalization could already be observed within the N2 time window (190–350 ms), while the first reliable effect of lexical tone normalization on cortical processing was observable only from the P3 time window (220–500 ms) onwards. The ERP patterns demonstrate that the contrastive perceptual normalization of lexical tones and that of vowels occur at least in partially separate time windows. This suggests that the extrinsic normalization can operate at the level of phonemes and tonemes separately instead of operating on the whole syllable at once.

Time Course of Normalization of Functional β-Cell Capacity in the Diabetes Remission Clinical Trial After Weight Loss in Type 2 Diabetes.

To assess functional β-cell capacity in type 2 diabetes during 2 years of remission induced by dietary weight loss. A Stepped Insulin Secretion Test with Arginine was used to quantify functional β-cell capacity by hyperglycemia and arginine stimulation. Thirty-nine of 57 participants initially achieved remission (HbA1c <6.5% [<48 mmol/mol] and fasting plasma glucose <7 mmol/L on no antidiabetic drug therapy) with a 16.4 ± 7.7 kg weight loss and were followed up with supportive advice on avoidance of weight regain. At 2 years, 20 participants remained in remission in the study. A nondiabetic control (NDC) group, matched for age, sex, and weight after weight loss with the intervention group, was studied once. During remission, median (interquartile range) maximal rate of insulin secretion increased from 581 (480-811) pmol/min/m2 at baseline to 736 (542-998) pmol/min/m2 at 5 months, 942 (565-1,240) pmol/min/m2 at 12 months (P = 0.028 from baseline), and 936 (635-1,435) pmol/min/m2 at 24 months (P = 0.023 from baseline; n = 20 of 39 of those initially in remission). This was comparable to the NDC group (1,016 [857-1,507] pmol/min/m2) by 12 (P = 0.064) and 24 (P = 0.244) months. Median first-phase insulin response increased from baseline to 5 months (42 [4-67] to 107 [59-163] pmol/min/m2; P < 0.0001) and then remained stable at 12 and 24 months (110 [59-201] and 125 [65-166] pmol/min/m2, respectively; P < 0.0001 vs. baseline) but lower than that of the NDC group (250 [226-429] pmol/min/m2; P < 0.0001). A gradual increase in assessed functional β-cell capacity occurred after weight loss, becoming similar to that of NDC group participants by 12 months. This result was unchanged at 2 years with continuing remission of type 2 diabetes.

Talker normalization in typical Cantonese-speaking listeners and congenital amusics: Evidence from event-related potentials.

Despite the lack of invariance in the mapping between the acoustic signal and phonological representation, typical listeners are capable of using information of a talker's vocal characteristics to recognize phonemes, a process known as “talker normalization”. The current study investigated the time course of talker normalization in typical listeners and individuals with congenital amusia, a neurodevelopmental disorder of refined pitch processing. We examined the event-related potentials (ERPs) underling lexical tone processing in 24 Cantonese-speaking amusics and 24 typical listeners (controls) in two conditions: blocked-talker and mixed-talker conditions. The results demonstrated that for typical listeners, effects of talker variability can be observed as early as in the N1 time-window (100–150 ms), with the N1 amplitude reduced in the mixed-talker condition. Significant effects were also found in later components: the N2b/c peaked significantly earlier and the P3a and P3b amplitude was enhanced in the blocked-talker condition relative to the mixed-talker condition, especially for the tone pair that is more difficult to discriminate. These results suggest that the blocked-talker mode of stimulus presentation probably facilitates auditory processing and requires less attentional effort with easier speech categorization than the mixed-talker condition, providing neural evidence for the “active control theory”. On the other hand, amusics exhibited comparable N1 amplitude to controls in both conditions, but deviated from controls in later components. They demonstrated overall later N2b/c peak latency significantly reduced P3a amplitude in the blocked-talker condition and reduced P3b amplitude irrespective of talker conditions. These results suggest that the amusic brain was intact in the auditory processing of talker normalization processes, as reflected by the comparable N1 amplitude, but exhibited reduced automatic attentional switch to tone changes in the blocked-talker condition, as captured by the reduced P3a amplitude, which presumably underlies a previously reported perceptual “anchoring” deficit in amusics. Altogether, these findings revealed the time course of talker normalization processes in typical listeners and extended the finding that conscious pitch processing is impaired in the amusic brain.

Extrinsic talker normalization via rapid accumulation of talker-specific phonetic detail

Talker normalization makes speech processing more efficient by reducing the degrees of freedom between the highly variable acoustic realization of speech and its abstract mental representation. However, it is unknown how processing gains afforded by talker normalization depend on the amount of talker-specific information available in the preceding speech context. We explored the timecourse of extrinsic talker normalization in a series of speeded classification tasks that parametrically varied the amount of talker-specific phonetic detail available in the preceding speech context. In single- and mixed-talker conditions, listeners identified a target word (either “boot” or “boat”) preceded by either no speech context, a short carrier phrase (“It's a...”), or a long carrier phrase (“I owe you a...”) spoken by the same talker as the target word. Listeners' word identification was always slower in the mixed-talker condition than the single-talker one. However, the amount of interference decreased as the amount of preceding speech context increased: the interference effect of the mixed-talker condition was greatest with no carrier, less with a short carrier, and least in the long-carrier condition. These results reveal how extrinsic talker normalization facilitates speech processing via rapid accumulation of talker-specific detail from the speech context.

Achieving constancy in spoken word identification: Time course of talker normalization

This event-related potential (ERP) study examines the time course of context-dependent talker normalization in spoken word identification. We found three ERP components, the N1 (100–220ms), the N400 (250–500ms) and the Late Positive Component (500–800ms), which are conjectured to involve (a) auditory processing, (b) talker normalization and lexical retrieval, and (c) decisional process/lexical selection respectively. Talker normalization likely occurs in the time window of the N400 and overlaps with the lexical retrieval process. Compared with the nonspeech context, the speech contexts, no matter whether they have semantic content or not, enable listeners to tune to a talker’s pitch range. In this way, speech contexts induce more efficient talker normalization during the activation of potential lexical candidates and lead to more accurate selection of the intended word in spoken word identification.

Molecular Signature of Smoking in Human Lung Tissues

Cigarette smoking is the leading risk factor for lung cancer. To identify genes deregulated by smoking and to distinguish gene expression changes that are reversible and persistent following smoking cessation, we carried out genome-wide gene expression profiling on nontumor lung tissue from 853 patients with lung cancer. Gene expression levels were compared between never and current smokers, and time-dependent changes in gene expression were studied in former smokers. A total of 3,223 transcripts were differentially expressed between smoking groups in the discovery set (n = 344, P < 1.29 × 10(-6)). A substantial number of smoking-induced genes also were validated in two replication sets (n = 285 and 224), and a gene expression signature of 599 transcripts consistently segregated never from current smokers across all three sets. The expression of the majority of these genes reverted to never-smoker levels following smoking cessation, although the time course of normalization differed widely among transcripts. Moreover, some genes showed very slow or no reversibility in expression, including SERPIND1, which was found to be the most consistent gene permanently altered by smoking in the three sets. Our findings therefore indicate that smoking deregulates many genes, many of which reverse to normal following smoking cessation. However, a subset of genes remains altered even decades following smoking cessation and may account, at least in part, for the residual risk of lung cancer among former smokers. Cancer Res; 72(15); 3753-63. ©2012 AACR.

Prevalence of C-Reactive Protein Elevation and Time Course of Normalization in Acute Pericarditis

Background— The role of inflammatory markers is not well defined for either diagnosis or treatment of pericarditis. The aim of this study is to prospectively evaluate the frequency of high-sensitivity C-reactive protein (hs-CRP) elevation in patients with acute pericarditis, its time course of normalization, and the possible importance for diagnosis, therapy, and prognosis. Methods and Results— Two hundred consecutive patients with viral or idiopathic acute pericarditis (mean age, 53±15.5 years; 103 men) were studied from August 2005 to August 2007 in 2 Italian referral centers. Hs-CRP was determined at presentation and then every week until normalization. Hs-CRP elevation was recorded in 156 of 200 cases (78%) at presentation. Recognized causes of a negative hs-CRP at presentation were early assessment in 15 of 44 cases (34%) and previous anti-inflammatory therapies in 22 of 44 cases (50%). Hs-CRP normalization was achieved with the following time course: 120 of 200 (60%) at week 1, 170 of 200 (85%) at week 2, 190 of 200 (95%) at week 3, and all cases (100%) at week 4. In multivariable analysis, incomplete response to empirical anti-inflammatory therapy at week 1 (hazard ratio, 2.98; 95% confidence interval, 1.80 to 4.94; P &lt;0.001), corticosteroid therapy (hazard ratio, 2.80; 95% confidence interval, 1.59 to 4.95; P &lt;0.001), and the presence of elevated hs-CRP at week 1 (hazard ratio, 2.36; 95% confidence interval, 1.32 to 4.21; P =0.004) were independent risk factors for recurrence. Conclusions— Hs-CRP is elevated at the initial presentation in ≈3 of 4 cases of acute pericarditis, identifies patients at higher risk of recurrence, and could be used to monitor disease activity and select appropriate therapy length.

Rapid Initial Reduction of Hyperenhanced Myocardium After Reperfused First Myocardial Infarction Suggests Recovery of the Peri-Infarction Zone

Background— The time course and magnitude of infarct involution, functional recovery, and normalization of infarct-related electrocardiographic (ECG) changes after acute myocardial infarction (MI) are not completely known in humans. We sought to explore these processes early after MI and during infarct-healing using cardiac MRI. Methods and Results— Twenty-two patients with reperfused first-time MI were examined by MRI and ECG at 1, 7, 42, 182, and 365 days after infarction. Global left ventricular function and regional wall thickening were assessed by cine MRI, and injured myocardium was depicted by delayed contrast-enhanced MRI. Infarct size by ECG was estimated by QRS scoring. The reduction of hyperenhanced myocardium occurred predominantly during the first week after infarction (64% of the 1-year reduction). Furthermore, during the first week the amount of nonhyperenhanced myocardium increased significantly ( P &lt;0.001), although the left ventricular mass remained unchanged. Left ventricular ejection fraction increased gradually, whereas the greater the regional transmural extent of hyperenhancement at day 1, the later the recovery of regional wall thickening. Regional wall thickening decreased progressively with increasing initial transmural extent of hyperenhancement ( P trend &lt;0.0001). The time course and magnitude of decrease in QRS score corresponded with the reduction of hyperenhanced myocardium. Conclusions— The early reduction of hyperenhanced myocardium may reflect recovery of hyperenhanced, reversibly injured myocardium, which must be considered when predicting functional recovery from delayed contrast-enhanced MRI findings early after infarction. Also, the time course and magnitude for reduction of hyperenhanced myocardium were associated with normalization of infarct-related ECG changes.

Restoration of the cellular thiol status of peritoneal macrophages from CAPD patients by the flavonoids silibinin and silymarin

During continuous ambulatory peritoneal dialysis (CAPD) the peritoneal immune cells, mainly macrophages, are highly compromised by multiple factors including oxidative stress, resulting in a loss of functional activity. One reason for the increase of inflammatory reactions could be an imbalance in the thiol-disulfide status. Here, the possible protective effects of the antioxidant flavonoid complex silymarin and its major component silibinin on the cellular thiol status were investigated. Peritoneal macrophages from dialysis fluid of 30 CAPD patients were treated with silymarin or silibinin up to 35 days.A time-dependent increase of intracellular thiols was observed with a nearly linear increment up to 2.5-fold after 96 hours, reaching a maximum of 3.5-fold after 20 days of culture. Surface-located thiols were also elevated. The stabilization of the cellular thiol status was followed by an improvement of phagocytosis and the degree of maturation as well as significant changes in the synthesis of IL-6 and IL-1ra. Furthermore, the treatment of peritoneal macrophages with flavonoids in combination with cysteine donors resulted in a shortened and more efficient time course of thiol normalization as well as in a further increased phagocytosis. In addition, GSH-depletion in thiol-deficient media simulating CAPD procedures led to intracellular thiol deficiency similar to the in vivo situation.It is concluded that treatment with milk thistle extracts silymarin and silibinin alone or, more effectively in combination with cysteine donors, provide a benefit for peritoneal macrophages of CAPD-patients due to a normalization and activation of the cellular thiol status followed by a restoration of specific functional capabilities.

THE HETEROGENEOUS AND DELAYED COURSE OF BLOOD PRESSURE NORMALIZATION IN HYPERTENSIVE PATIENTS AFTER BILATERAL NEPHRECTOMY WITH AND WITHOUT SUBSEQUENT RENAL TRANSPLANTATION

CONDENSED ABSTRACTControversy exists about the time course of blood pressure normalization in hypertensive patients after bilateral nephrectomy. The course of blood pressure was retrospectively assessed in 14 hypertensive patients. Bilateral nephrectomy resulted in a decrease of blood pressure within 6 months following surgery. Combined antihypertensive medication was necessary in most patients with renovascular hypertension even after bilateral nephrectomy. Subsequent renal transplantation following bilateral nephrectomy caused de novo increase in blood pressure in formerly hypertensive patients.Background. Controversy exists about the time course of blood pressure normalization following bilateral nephrectomy. We sought to evaluate the time course of blood pressure normalization following bilateral nephrectomy and after subsequent kidney transplantation.Methods and Results. Clinical data from 14 hypertensive patients were retrospectively assessed. Baseline blood pressure was 175 ± 33/109 ± 9 mmHg. Ten patients firstly underwent unilateral nephrectomy, which resulted in a slight increase of blood pressure (185 ± 22/110 ± 5 mmHg). One month following bilateral nephrectomy, blood pressure was 167 ± 23/104 ± 17 mmHg, at 3 months 159 ± 42/104 ± 25 mmHg, and at 6 months 149 ± 41/96 ± 30 mmHg. Antihypertensive medication was necessary in 9/14 patients at a 2 year follow-up. Eight patients remained anephric (group I), 6 patients had subsequent kidney transplantation (group II). In group I, blood pressure was 159 ± 42/93 ± 17 mmHg and 129 ± 34/75 ± 14 mmHg at 3 and 6 months, respectively (p < 0.05 vs. baseline). In group II, blood pressure decreased from 188 ± 42/128 ± 46 mmHg to 167 ± 48/113 ± 32 mmHg at 3 months, but increased after tansplantation to 186 ± 39/118 ± 33 mmHg. Antihypertensive medication was still necessary in 5 transplanted patients (83%) and in 3 anephric patients (38%).Conclusion. Adaptation of the blood pressure response following bilateral nephrectomy is a time requiring process, and long-term antihypertensive medication may still be necessary.

Steps toward recovery of function after hemilabyrinthectomy in frogs

Removal of the labyrinthine organs on one side results in a number of severe postural and dynamic reflex deficits. Over time some of these behavioral deficits normalize again. At a chronic stage the brain of frogs exhibits a number of changes in vestibular and propriospinal circuits on the operated side that were studied in vitro. The onset of changes in the vestibular nuclear complex was delayed, became evident only after head posture had recovered by more than 50%, and was independent of the presence or absence of a degeneration of vestibular nerve afferent fibers. The time course of changes measured in the isolated spinal cord paralleled the time course of normalization of head and body posture. Results obtained after selective lesions of individual labyrinthine nerve branches show that unilateral inactivation of utricular afferent inputs is a necessary and sufficient condition to provoke postural deficits and propriospinal changes similar to those after the removal of all labyrinthine organs. The presence of multiple synaptic changes at distributed anatomic sites over different periods of time suggests that different parts of the central nervous system are involved in the normalization of different manifestations of the vestibular lesion syndrome. (Otolaryngol Head Neck Surg 1998;119:27-33.)

Comparison of Passive Stiffness Variables and Range of Motion in Uninvolved and Involved Ankle Joints of Patients Following Ankle Fractures

The purpose of this study was to quantify several variables of ankle stiffness and dorsiflexion (DF) range of motion (ROM) in the casted (fractured) and noncasted ankles of humans after cast removal. Thirty subjects (mean age = 32.4 years, SD = 15.8) with malleolar ankle fractures were tested within 4 days of cast removal but before they began physical therapy. A torque motor system generated torque-versus-displacement graphs by recording angular displacement and resistive torque during a 6 0/s passive cycling of the ankle from 10 degrees of plantar flexion to the limit of DF ROM: Maximum passive DF ROM, passive torque, and passive elastic stiffness at the neutral position and energy loss were measured. Testing was performed in the absence of triceps surae muscle electromyographic activity. For analysis, subjects were separated into two groups based on fracture severity. There was no difference in passive torque between the fractured ankles and the matched noncasted ankles. There was a small difference in passive elastic stiffness between the more severely fractured ankles and the matched noncasted ankles. The fractured ankles were different in terms of energy loss from the matched noncasted ankles. For maximum passive DF ROM, there was a large difference between the fractured ankles (more severe: mean = 4.4 degrees; less severe: mean = 6.8 degrees) and the matched noncasted ankles (more severe: mean = 15.1 degrees; less severe: mean = 19.1 degrees). Altered length-tension relationships and neuromuscular mechanisms have been suggested to produce postimmobilization joint contractures. The results of this study on humans are consistent with both possibilities and support the theory that changes that occur during immobilization result in protection from overstretching of the fragile calf musculature after a period of ankle fixation. The time course of normalization of stretch reflexes warrants investigation.

Normalization of Left Ventricular Ejection Fraction Following Resection of Pheochromocytoma in a Patient with Dilated Cardiomyopathy

Catecholamine-induced cardiomyopathy associated with pheochromocytoma is a well-recognized but rare entity. Both hypertrophic and dilated variants have been described. We report a case of dilated cardiomyopathy associated with a benign pheochromocytoma that showed complete normalization of left ventricular systolic function following removal of the tumor. Serum noradrenaline and dopamine were significantly elevated without elevation in serum adrenaline levels. This may be the first report in which radionuclide ventriculography was used to document the time course of normalization in LVEF following removal of a pheochromocytoma.

Transmembrane ion balance in slowly and rapidly adapting lobster stretch receptor neurones.

The transmembrane exchange of Na+, K+, and Cl- in slowly and rapidly adapting lobster stretch receptor neurones was studied using ion-sensitive microelectrodes in combination with conventional electrophysiological techniques. The investigation was founded on the assumption that the transmembrane ion exchange is accomplished by active and passive transports which add up to zero in steady state for each ion involved. The active transports are assumed to include Na+ and K+ transports driven by an electrogenic Na-K pump. To these transports are also added equimolar fluxes of K+ and Cl- leaking from the impaling micro-electrode. The passive transports are assumed to pass through membrane channels in accordance with constant field kinetics. For a quantitative evaluation of the transmembrane ion exchange in resting conditions measurements were made of the resting concentrations of Na+, K+ and Cl-; the voltage dependence of the ungated leak current; and ouabain-induced changes in resting membrane current and intracellular ion concentrations. From the results it follows that both the resting pump current and the leak permeabilities for the ions investigated have values which do not seem to differ between slowly and rapidly adapting receptor neurones. For a quantitative evaluation of the relation between internal Na+ and pump current production, measurements were made of the outward membrane current as a function of internal Na+ and K+ following a shift of these ions by means of prolonged repetitive impulse activation. It was found that the investigated relation is compatible with Garay-Garrahan kinetics (Garay & Garrahan, 1973) in both receptor neurones, but the results imply a larger maximum Na+-extrusion capacity in slowly than in rapidly adapting cells. From recordings of the time course of post-tetanic normalization of both the membrane current and intracellular Na+ concentration, cell volume values could be deduced which were closely similar in slowly and rapidly adapting receptors. A corresponding similarity was also found for the cell area which was derived from membrane capacitance measurements.

Recovery of function and basal ganglia [ 14C]2-deoxyglucose uptake after nigrostriatal injury

Rats with unilateral 6-hydroxydopamine injections along the mesotelencephalic dopaminergic projection showed a profound impairment in localizing somatosensory stimuli on the contralateral body surface at 3 days postoperatively. Approximately one-half of the affected animals recovered the ability to localize tactile stimuli during 6 weeks postoperatively, whereas the remainder did not. When it occurred, the recovery of sensorimotor function began between the third and fifth day postoperatively and plateaued between days 14 and 21. Unilateral damage to these dopaminergic neurons resulted in hemispheric asymmetries of [ 14C]2-deoxyglucose incorporation at 3 days postoperatively. For structures that normally receive a dopaminergic innervation (e.g., neostriatum, nucleus accumbens septi, olfactory tubercle) the autoradiographic density of the injured side was decreased relative to the intact hemisphere. For structures that receive striatal inputs (globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata), the autoradiographic density was increased on the side of the injury. This pattern of altered [ 14C]2-deoxyglucose incorporation was still present at 6 weeks postoperatively in animals that showed no recovery of somatosensory localization during that time. In contrast, rats that did recover showed no hemispheric asymmetries within the anterior neostriatum, globus pallidus, or substantia nigra pars reticulata at 6 weeks postoperatively, and the time course of normalization of metabolic activity in these structures was similar to that for behavioral restoration. These results directly demonstrate the importance of the neostriatum and particular structures efferent to it in the recovery of sensorimotor functions after striatal dopamine depletion. The types of neuronal plasticity within this basal ganglia circuitry responsible for the normalization of [ 14C]2-deoxyglucose incorporation and behavior are discussed.

Increased serum prolactin levels during phenothiazine and butyrophenone treatment of six postpartum women

(1) Serum prolactin levels of six women, who developed psychoses during the postpartum period and were treated with neuroleptic drugs, were higher than those of a group of non-postpartum women of comparable age treated with similar doses of these drugs. (2) The magnitude of the neuroleptic-induced elevations in serum prolactin diminished with time during the postpartum period and returned to that found in non-parturient drug-treated females approximately 120 days postpartum. (3) A similar increased responsiveness of the hypothalamic-pituitary axis controlling prolactin secretion in postpartum females is manifested by the suckling response and increased prolactin response to thyrotrophin releasing hormone (TRH). The time course of normalization of these enhanced endocrine responses is roughly similar to that found for normalization of the prolactin response to neuroleptic drugs. A common mechanism may underlie each of these phenomena.