Changes In Tone Research Articles

Эволюция политики “стратегической неопределенности” США в тайваньском вопросе

The article is dedicated to the analysis of “strategic ambiguity” concept – a tool of U.S. foreign policy aimed at dual deterrence of both mainland China and breakaway Taiwan. Washington stayed deliberately ambiguous in its commitments to defend Taiwan thus leaving Beijing uncertain whether the U.S. will intervene in case of escalation in the Strait, and at the same time not encouraging Taiwanese authorities to declare full independence and sovereignty which would provoke military escalation with mainland China, dragging the U.S. into full-scale conflict with the Chinese People’s Liberation Army (PLA). The article analyzes the roots of this approach during D. Eisenhower’s years in office, its evolution en course and after the Cold War, and its erosion under D. Trump and J. Biden. The article shows that the U. S. President Eisenhower wished to maintain status-quo in Taiwan Strait, fearing that he would either have to turn a blind eye on the communist takeover of Taiwan, or be dragged into conflict with the close ally of Moscow, which would eventually lead to the war with the USSR. Eisenhower and his administration remained ambiguous in their communications with the PRC (mainland China) and Taiwan, not encouraging the island to declare full independence and at the same time not giving Beijing a carte blanche for military intervention. This approach dubbed in political science and international relations theory as “strategic ambiguity” proved to be useful, and was reinforced during Washington–Beijing rapprochement in 1970s. Under Trump administration, the U.S. started to consider dropping the “strategic ambiguity” policy towards clearer deterrence commitments. This trend manifested via emotional statements made by Donald Trump himself, mostly on social media, as well as through a change of tone in key foreign policy documents and new decisions that signaled a serious revision of the American approach to military cooperation between the United States and Taiwan. This trend continued and exacerbated under Biden administration due to number of bills signed, including the Taiwan Enhanced Resilience Act (TERA) which de-facto dubbed the contested island as Washington’s “Major Non-NATO Ally” and enabled to boost military supplies. The erosion of the “strategic ambiguity” policy also manifested through various high-profile contacts, including the House Speaker Nancy Pelosi’s visit on the island.

РЕГУЛЯЦИЯ МОЗГОВОГО КРОВООБРАЩЕНИЯ ПРИ КОГНИТИВНОЙ ДЕЯТЕЛЬНОСТИ ЧЕЛОВЕКА. ЭКСПЕРИМЕНТ «МАРС-500»

Investigation of cerebral arterial circulation during cognitive testing was performed before and after prolonged isolation of 6 healthy subjects imitating a mission to space. The ultrasonic technique was used to measure linear blood velocity (LBV) in the medial cerebral artery (MCA) in the course of verbal and tactile testing. Analysis of MCA LBV both before and after isolation showed that at rest and during testing blood flow changes were equally wave-like; however, the amplitude made a significant increase at testing. It was found that LBV fluctuations occurred within the low-frequency band (LFB) and were consistent with the regular changes in tone of resistive vessels, primarily due to own myogenic activity. The wave-like LBV dynamics was observed over all testing time in all the subjects irrespective of central hemodynamics and respiration parameters. Analysis of LBV dynamics revealed a reliable seasonal (periodic) component supporting to the wave-like LBV fluctuations during testing. At large, prolonged isolation did not influence cerebral circulation much but for the reaction to the verbal testing after isolation completion when we registered a reliable rise of the LFB amplitude in left CMA due to activation of the left hemisphere resulting from specifics of communication in a small isolated group. We assume that the wave-like blood flow in cerebral vessels is an adaptive mechanism of autoregulation capable to meet the metabolic demand of the brain during cognitive testing and protect from local hyperthermia.

The boundary-induced modulation of obstruents and tones in Thai

Limited studies have suggested that tones can be strengthened in domain-initial positions, suggesting that domain-initial strengthening (DIS) effects in a tone language extend beyond the first segment of a prosodic domain. However, these studies have yielded unclear results. This study investigated whether DIS causes boundary-induced changes in tones. This study analyzed the maximum fundamental frequency (f0) of the falling, mid, and low tones in Thai along with acoustic measures of consonants, including the Voice Onset Times (VOTs) of /b/, /p/, and /pʰ/, frication duration of /f/, and consonant-induced f0 perturbation effects associated with these four consonants in domain-initial and domain-medial positions. Some evidence of DIS effects on tones was found, suggesting that DIS effects in a tone language can extend to tone production realized with the vowel that is beyond the first segment. Additionally, the VOTs of /b/, /p/, and /pʰ/ were more negative, unchanged, and longer, respectively, the frication of /f/ was longer, and f0 following /pʰ/ was raised in a domain-initial position compared to a domain-medial position. The findings contribute to the current understanding of the prosody-phonetics interface, particularly with respect to the relationship between DIS and the realization of tones.

What is known about changes in pelvic floor muscle strength and tone in women during the childbirth pathway? A scoping review.

This scoping review aims to comprehensively explore the existing research on the changes in pelvic floor function that occur throughout the childbirth pathway (antenatal, intrapartum, and postnatal period). Furthermore, it seeks to identify new opportunities and directions for future research in this field. In particular, this review focuses on investigating pelvic floor muscle strength and tone in women during the childbirth pathway. The following databases were investigated from their inception: PubMed, OVID, Medline, ScienceDirect, The Cochrane Central Library, Scopus, Web of Science, PEDro, Scholar Google, Embase, and CINHAIL. Literature research was carried out from March to October 2022. Records identified through database searching were imported to Covidence. According to Arksey and O'Malley's five-stage scoping review framework, researchers screen titles and abstracts for eligibility and exclude records that do not meet the inclusion criteria. A total of 40 studies were included in the data extraction phase. These articles underwent a review, with a specific emphasis on examining the tone, strength, and distensibility of the pelvic floor throughout the childbirth pathway. Among the selected studies, 22 investigated pelvic floor strength, 7 the distensibility, and 3 articles the tone. This review identified both areas of agreement and disagreement across all three themes examined, with a particular emphasis on labor and the postpartum period. Notably, the review unveiled a significant scarcity of data concerning the tone of pelvic floor muscles throughout the childbirth pathway. Further studies to investigate the relationship between midwifery care and pelvic floor outcomes are required to improve clinical practice.

Para table tennis improves psychological/mental and cardiovascular health in individuals with spinal cord injury.

Although rehabilitation exercise is known to be beneficial for cardiovascular and mental health, it remains a daunting challenge for patients with spinal cord injury (SCI) who rely on wheelchairs for mobility. This study aimed to examine the effectiveness of a 4-week para table tennis program in enhancing self-efficacy and health outcomes in adults with SCI. A total of 39 SCI patients were included and divided into the experimental group (n = 18, a 4-week para table tennis training program) and the control group (n = 21). Frequency domain indices of heart rate variability (HRV) were used to evaluate the function of the autonomic nervous system. Following para table tennis training, there was a significant reduction in the physical stress index (PSI, P < 0.001), accompanied by shifts in autonomic regulation of vagal dominance. Additionally, the para table tennis training led to significant improvements in vessel state, differential pulse wave index, atrial elasticity, eccentric constriction power, remaining blood volume, and self-efficacy (all P < 0.05). Para table tennis training results in favorable changes in sympathetic tone, enhanced self-efficacy, improved cardiovascular well-being, and an overall positive transformation in HRV.

Objective Evaluation of Local Muscle Fatigue in Cerebral Palsy Using A Gait Corrector

The participants were seven individuals (age range 7–36 years) whose walking ability ranged from independent to requiring assistance with a cane, walker, etc. The protocol consisted of resting for at least five minutes before starting to walk, wearing a Gait Corrector device, and walking with light and heavy loads based on the participant's rating of perceived exertion (RPE), followed by resting for 10 minutes before the end of the protocol.Near-infrared spectroscopy (NIRS) electrodes were attached bilaterally to the tibialis anterior and lateral gastrocnemius muscles. NIRS was used to measure blood oxygenation dynamics in local muscles from rest before walking to 10 minutes after walking, and evoked electromyography was used to measure the nerve conduction velocity of the peripheral nerves before and during early and late walking.The tone state of the lateral gastrocnemius muscle was measured three times using an evoked potential-testing device: before walking, immediately after heavy-load walking, and 10 minutes after walking. A recording electrode was attached to the abductor digitorum medialis muscle and a reference electrode was attached to the base of the toe. The M and F waves were recorded using tibial nerve stimulation. The average F/M ratio was used as a parameter of the F-wave.Regarding the change in muscle tone, four of the seven patients exhibited no change or a lower mean F/M ratio after walking than before walking, whereas three patients who exhibited resistance to other dorsiflexion movements of the ankle joint had higher values. Blood oxygenation dynamics revealed a greater disparity between oxyhemoglobin and deoxyhemoglobin concentrations after walking in all participants, suggesting local muscle fatigue, the degree of which showed no improvement even after 10 minutes of rest.

Functional Assessment of Patients after Hip and Knee Arthroplasty – Preliminary Studies

Osteoarthritis is one of the main causes of pain and functional disorders in society, one that often affects the performance of everyday activities. The treatment usually consist of physiotherapy and pharmacotherapy, while in advanced stages, surgical treatment is required. The common method to assess the effectiveness of treatment is the physical examination by standardized scales of quality of life, assessment of pain and functioning. More recently, advances in objective assessment tools have been included such as DIERS formetric III 4D, myotometry or bioimpedance. The aim of the study is to evaluate the functional assessment of patients after hip and knee arthroplasty performed due to osteoarthritis. Hip and knee arthroplasty clearly improves the functioning of patients, reduces the intensity of pain and the risk of falls. In addition, changes in muscle tone and stiffness were demonstrated before and after the arthroplasty of the lower limbs.

“DISGRACE” BY J.M. COETZEE AS A POSTMODERN VARIATION OF THE NOVEL ABOUT A MUSICIAN

“DISGRACE” BY J.M. COETZEE AS A POSTMODERN VARIATION OF THE NOVEL ABOUT A MUSICIAN

Professional and amateur: two vocal interpretations of the same poem.

This article concerns two vocal interpretations of the poem Dwa wiatry (Two Winds) by Julian Tuwim: one comes from an actor, the other from an amateur publishing educational materials on the Internet. The aim is to explain why the actor’s interpretation seems more suggestive than the amateur one. The subject of the study is the prosodic features of both performances of the poem (tempo, sound intensity, and tone changes), treated as an iconic indicator of its cognitive and emotional content. This article is a continuation of an earlier publication in which Tuwim’s Lokomotywa (Locomotive) was examined in a similar way. In both studies, the Praat programme for acoustic analysis of sound was used for research.

Effects of L-Dopa, SKF-38393, and quinpirole on exploratory, anxiety- and depressive-like behaviors in pubertal female and male mice

Adolescence is a phase of substantial changes in the brain, characterized by maturational remodeling of many systems. This remodeling allows functional plasticity to adapt to a changing environment. The dopaminergic system is under morphological and physiological changes during this phase. In the present study, we investigated if changes in the dopaminergic tone alter mice behavior in a receptor and sex-specific manner, specifically at the beginning of the puberty period. We administered L-Dopa, SKF-38393 (D1 dopamine receptor agonist), and Quinpirole (D2 dopamine receptor agonist) and tested male and female mice's motor, anxiety- and depressive-like behavior. While females displayed an impaired exploratory drive, males presented an intense depressive-like response. Our results provide insights into the function of dopaminergic development in adolescent behavior and highlight the importance of studies in this time window with male and female subjects.

An investigation of cardiac vagal tone over time and its relation to vigilance performance: a growth curve modeling approach.

Research over the last couple of decades has demonstrated a relationship between psychophysiological measures, specifically cardiac functions, and cognitive performance. Regulation of the cardiac system under parasympathetic control is commonly referred to as cardiac vagal tone and is associated with the regulation of cognitive and socioemotional states. The goal of the current study was to capture the dynamic relationship between cardiac vagal tone and performance in a vigilance task. We implemented a longitudinal growth curve modeling approach which unveiled a relationship between cardiac vagal tone and vigilance that was non-monotonic and dependent upon each person. The findings suggest that cardiac vagal tone may be a process-based physiological measure that further explains how the vigilance decrement manifests over time and differs across individuals. This contributes to our understanding of vigilance by modeling individual differences in cardiac vagal tone changes that occur over the course of the vigilance task.

EFFECTIVENESS OF PHYSICAL THERAPY AND REHABILITATION IN IMPROVING MOTOR SKILLS AND MENTAL FUNCTION IN CHILDREN WITH CEREBRAL PALSY

Cerebral palsy was first described by William John Little in 1846. There are many definitions of cerebral palsy that vary from author to author. However, we can say that cerebral palsy (CP) is a chronic non-progressive brain damage, postural and body motility disorder. Apart from sensorimotor abnormalities, some cases are accompanied by mental disorders as well as disorders of cognitive functions. It can occur during pregnancy, at birth or during the postnatal period, ie. prenatal, perinatal and postnatal - equally in both sexes. There are different classifications of cerebral palsy: according to changes in muscle tone, according to topographic features and according to the severity of the clinical picture.According to changes in muscle tone, they are divided into: Spastic form, Athetoid form, Ataxic form, Hypotonic form and Mixed form. According to the topography they are classified as: Diplegia, Quadriplegia, Hemiplegia, Triplegia and Monoplegia Physical therapy program is determined based on the clinical form of the disease. When determining a rehabilitation program, the principle of an individual approach is followed. Rehabilitation includes: physical medicine, kinesitherapy, reflex exercises according to Vojta, manual massage, thermotherapy, education of parents for rehabilitation at home; orthopedic aids; special education techniques. The aim of this study is to determine the role and impact of Physical Medicine and Rehabilitation in the treatment of children with Cerebral Palsy in early childhood. The research was conducted at the University of Southeast Europe - (Stul University) at the Faculty of Health Sciences in the Department of Physical Therapy and Rehabilitation, over a period of 6 months, from the beginning of April to the end of September 2023. 61 patients with cerebral palsy are included in the research, of which 28 are male, and the remaining 33 patients are female. The patients included in the research are classified into groups according to: gender, age and clinical form of cerebral palsy. The treatment of Cerebral Palsy (CP) has a complex character and includes medical, pedagogical and social rehabilitation. The individual tasks of the rehabilitation are determined after a functional examination of the motor abilities, where the main role is played by muscle tone, normal and pathological reflex motor activity, in the period up to 1 year of age. The goal of treatment with Physical Therapy and Rehabilitation is to achieve correct and timely development of movements and correction of pathological movement stereotypes (models), which occurred as a result of brain tissue damage. As for the motor deficit, kinesitherapy plays a major role. Established modern methods for kinesitherapy are the specialized methods for neuromuscular re-education of Vojta and Bobath. The Rood and Rabat methods werw also be used to facilitate the required movements and train coordination. Physical therapy and rehabilitation combined with kinesitherapy have an exceptional positive effect in: prevention of pathological primitive reflexes;creation and automation of normal active movements;saving irregular positions of the limbs and the whole body;establishment of balance and correct pattern of movement; fight against spasticity, secondary contractures and deformities; improvement of coordination and awareness of the body in relation to the environment.

All Hail, King Pippin!

Abstract Since shortly after its publication in 1957, The Short Reign of Pippin IV has been considered Steinbeck’s least characteristic work and is universally viewed as standing squarely at the bottom of his canon of fiction. This article argues for a reevaluation of the consensus view, arguing that Pippin is a crucial part of Steinbeck’s artistic oeuvre not only on its own merits but more importantly when viewed in literary sequence as his penultimate novel. Before his fictional work draws to a dissonant close in 1961, in Pippin Steinbeck draws a comparison to a musical coda that achieves an artistic effect of finality by altering the main themes of a movement through changes in tone, tempo, or key. Pippin is the last time Steinbeck expresses in fiction a fundamentally optimistic orientation toward the human condition,

Робототехнические средства реабилитации двигательной активности пациентов в постинсультном периоде

Stroke prevalence is one of the most acute problems in the medical and social aspects of society: strokes are the second most common in the mortality statistics of the population. In the Russian Federation, stroke occurs annually in almost 500,000 people and is the first among the causes of death from neurological diseases and the second most common cause of death after heart disease. The most common consequences of stroke are motor disorders of varying severity, manifested as changes in muscle tone, paresis and paralysis, and impaired walking function. This paper is an overview of the current state of robotic rehabilitation devices used for post-stroke limb paresis and of expected trends of their development. The existing variants of their construction, conditions of kinesiotherapy sessions for obtaining the greatest effect are considered. The authors are of the opinion that the nearest prospect for the development of high-tech devices of this type is not only complex stationary universal complexes for clinics, but also simple mobile specialized simulators with remote medical control for outpatient use.

The Role of Potassium Channels in the Regulation of the Transport Function of Rats Lymph Nodes during Inflammation

Lymph formed in tissues necessarily passes through lymph nodes (LN), which not only perform an immune function, but also take part in lymph flow through rhythmic high-amplitude contractions. During inflammation, inducible NO synthase (iNOS) is expressed in the lymph nodes, which promotes relaxation of the LN capsule. This study examined the role of KATP- and BKCa-channels in sepsis-induced LN remodeling. Sepsis was induced in rats by cecal ligation-puncture surgery. After 12 and 24 h, mesenteric LN were removed and examined in a myograph. KATP-channels were activated by pinacidil and blocked by glibenclamide. BKCa-channels blocked TEA and activated NS 1619. The strength of tonic contraction of the LN under the action of activators and blockers was assessed. LN of septic rats named low level of tone during standard stretching. Pinacidil led to greater relaxation of LN in septic rats compared to the control group; the effect of glibenclamide was accompanied by an increase in tone. Pinacidil combined with glibenclamide did not lead to significant changes in LN tone. The use of NS 1619 was accompanied by relaxation of the LN; in the LN of septic rats, the effect was more pronounced. TEA (3 mM) led to an increase in LN tone; the LN of septic rats responded to the use of TEA with a greater contraction. We concluded that NO produced by expressed iNOS in animals with sepsis directly or indirectly activates KATP- and BKCa-channels of smooth muscle cells of the capsule in the LN, which leading to hyperpolarization of the smooth muscle cell membrane and their relaxation, which that promotes relaxation of the LN capsule and their hypertrophy of LN. In the future, KATP- and BKCa-channels of smooth muscle cells of the lymph node LN capsule may be a potential target for therapeutic intervention to correct the immune response by slowing down or accelerating the flow of lymph through the LN.

Exploring cross-cultural and gender differences in facial expressions: a skin tone analysis using RGB Values

Facial expressions serve as crucial indicators of an individual's psychological state, playing a pivotal role in face-to-face communication. This research focuses on advancing collaboration between machines and humans by undertaking a thorough investigation into facial expressions. Specifically, we delve into the analysis of emotional variations related to changes in skin tone across different genders and cultural backgrounds (Black and white). The research methodology is structured across three phases. In Phase I, image data is acquired and meticulously processed from the Chicago face dataset, resulting in 12,402 augmented images across five classes (Normal case, Benign case, Adenocarcinoma, Squamous-cell-carcinoma, Large-cell-carcinoma). Phase II involves the identification of Regions of Interest (ROI) and the extraction of RGB values as features from these ROIs. Various methods, including those proposed by Kovac, Swift, and Saleh, are employed for precise skin identification. The final phase, Phase III, centers on the in-depth analysis of emotions and presents the research findings. Statistical techniques, such as Descriptive statistics, independent sample T-tests for gender and cross-cultural comparisons, and two-way ANOVA, are applied to RED, BLUE, and GREEN pixel values as response variables, with gender and emotions as explanatory variables. The rejection of null hypotheses prompts a Post Hoc test to discern significant pairs of means. The results indicate that both cross-cultural backgrounds and gender significantly influence pixel colors, underscoring the impact of different localities on pixel coloration. Across various expressions, our results exhibit a minimal 0.05% error rate in all classifications. Notably, the study reveals that green pixel color does not exhibit a significant difference between Anger and Neutral emotions, suggesting a near-identical appearance for green pixels in these emotional states. These findings contribute to a nuanced understanding of the intricate relationship between facial expressions, gender, and cultural backgrounds, providing valuable insights for future research in human–machine interaction and emotion recognition.

Phonetic Tonal Manifestations and Trends in Tone Change: A Case Study of the Yong-Deng Dialect in Northwest China

This study takes the Yong-deng dialect as a case study to investigate the phenomenon of tonal merging observed in Northwest Chinese dialects. It begins by examining the various monosyllabic tone patterns of the Yong-deng dialect, then supplements this with a review of the relevant literature, comparisons with the tone patterns of the neighbouring dialects, and an analysis of its tone sandhi in disyllabic and trisyllabic combinations. Each step of the dialect’s tonal variation is scrutinised, allowing for the identification of pertinent phonetic biases and the derivation of associated phonological rules. The central argument advanced here is that both synchronic tonal variation and diachronic tone change are governed by specific phonological rules. Despite the ostensibly variable phonetic manifestations, these rules can enable the prediction of the trajectory of tone change. The paper contributes to the understanding of tone merger and highlights its systemic and rule-bound nature.

Abstract 11632: Altered Autonomic Balance Linked to Arrhythmogenicity in Chronic Myocardial Infarction Ovine Model

Background: Increased sympathetic drive resulting in decreased heart rate variability (HRV), has been linked to cardiovascular diseases such as heart failure and myocardial infarction (MI). Dynamic electrophysiological changes due to acute ischemia and chronic MI are known to be pro-arrhythmic. Objective: Evaluate the changes in autonomic tone resulting from substrate remodeling during the development of chronic MI in an in-vivo ovine model. Methods: ECG recordings were collected at baseline, post occlusion and 6 weeks post MI, in young adult sheep (n=16). Time domain, frequency domain and non-linear measures of HRV were evaluated from 10 minutes of ECG data at the 3 time points. RR interval, heart rate, SDRR (standard deviation of the RR intervals), RMSSD (root mean square of successive differences between normal heartbeats), QTc interval, pNN 50 , LF/HF ratio and SD1/SD2 ratio were calculated and compared between baseline, post acute coronary artery occlusion and after 6 weeks of chronic MI. 24-hour telemetry was also performed in an ambulatory animal for 6 weeks to monitor the progression of alterations in the T-wave morphology or duration, i.e. T-wave alternans, a known marker of ventricular tachyarrhythmias, with chronic MI. Results: Chronic MI led to significantly decreased RR interval (Fig.1A) and increased heart rate (Fig.1B), along with a significant prolongation of the QTc interval (Fig.1C). Significant rise was also observed in the SDRR (Fig1D) and LF/HF ratio (Fig1E) indicating a shift towards increased sympathetic tone and reduced parasympathetic drive. In addition to the autonomic changes, a significant rise in T-wave alternans burden (Fig1F) and localized action potential alternans inducibility was observed with progression of MI indicating increased arrhythmogenicity. Conclusion: Skewed autonomic balance is evident in chronic MI and may be closely linked to increased arrhythmogenicity.

Abstract 11591: Mechanism of Finerenone-Induced Vasorelaxation in Arteries From Human Visceral Adipose Tissue

Introduction: Inadequate perfusion has emerged as a main determinant of adipose tissue (AT) dysfunction in obesity, sparking interest about possible ways to improve it. Among several mechanisms, mineralcorticoid receptor (MR) signaling has been shown to play a key role in the cross-talk between AT and the vasculature. Hypothesis: This study, therefore, tested the vasoactive properties of finerenone, a nonsteroidal MR antagonist, in arteries harvested from human AT. Methods: Small arteries (&lt;1 mm in diameter) were isolated from visceral AT and studied ex vivo in a wire myograph. After vessels had been contracted, changes in vascular tone were determined under different experimental conditions. Results: Finerenone elicited a concentration-dependent relaxation in arteries of obese individuals contracted with the thromboxane A2 analogue U46619 (n=9; P&lt;0001 vs. baseline); the steroidal MR antagonist potassium canrenoate, by contrast, did not induce any vasorelaxation (n=3; P&gt;0.05). The relaxing effect of finerenone on U46619-induced constriction was not different in arteries from lean (n=3) and obese subjects (P=0.155). Mechanistically, the vasorelaxing response to finerenone was not influenced by pre-incubation with the nitric oxide (NO) synthase inhibitor L-NAME (n=4; P=0.19 vs. saline), hence ruling out an involvement of NO. Interestingly, finerenone was also able to relax arteries contracted with endothelin-1 (n=7; P&lt;0.001) or with high-K + solution (n=4; P&lt;0001), as well as those contracted with the L-type Ca 2+ -channel agonist BayK8644 (n=5; P=0.007); similarly, the calcium-channel blocker nifedipine induced relaxation of arteries contracted with BayK8644 (n=3; P&lt;0.001). Conclusions: Finerenone induces NO-independent vasorelaxation in arterioles from human visceral AT, likely through antagonism of L-type Ca2 + -channels. This finding identifies a novel action of finerenone to improve AT perfusion, thereby potentially expanding the emerging observations about the cardiovascular benefits of this agent.

Integrity of the nucleus basalis of meynert and self-reported cognitive dysfunction during wearing-off periods in parkinson's disease.

Cognition in Parkinson's Disease can be impacted by the wearing-off phenomenon which results from changes in dopaminergic tone throughout the day. Given the well-established role of the cholinergic basal forebrain in cognition, we hypothesized that the Nucleus Basalis of Meynert may support cognitive processes during wearing-off periods. Specifically, we evaluated whether worsening of cognitive symptoms during wearing-off is more likely to occur with structural degeneration of the Nucleus Basalis of Meynert. Cognitive wearing-off was evaluated via the Movement Disorders Society Non-Motor Fluctuation Assessment Questionnaire in 33 Parkinson's Disease participants undergoing evaluation for deep brain stimulation. Pre-operative diffusion MRIs were used to measure brain diffusion metrics of the Nucleus Basalis of Meynert and control regions (caudate and putamen). The number of cognitive symptoms which worsened during OFF periods positively correlated with mean diffusivity (ρ = 0.561, p = 0.0007) and generalized fractional anisotropy (ρ=-0.447, p = 0.009) within the Nucleus Basalis of Meynert but not in the caudate or putamen. Meanwhile, stable cognitive symptoms, and ON-state cognitive performance as measured by the DRS-2 did not correlate with Nucleus Basalis of Meynert metrics. Correlations were corrected for age, sex, scanner type, disease duration, education and LEDD. Our study suggests that reduced structural integrity of the Nucleus Basalis of Meynert is associated with worsening of participant-reported cognitive deficits during OFF periods, but not overall cognitive functioning in the ON-state. These findings support the hypothesis that structural integrity of the cholinergic Nucleus Basalis of Meynert may provide resilience to cognitive worsening during dopamine-related wearing-off.