The fact and fallacy of immortality

Ye

Missing fundamental

The frequency-following response (FFR) is a scalp-recorded evoked potential which faithfully mimics an auditory stimulus waveform. Some research has attempted to relate the FFR to pitch perception based on FFR spectral peaks which correspond to the perceived pitch of the evoking stimulus, but these explanations are not definitive because the pitch of the evoking stimulus is often equal to the waveform envelope frequency or nonlinear distortion products also represented in the FFR. The experiments herein attempt to clarify the relevance of the FFR to pitch perception and as an assay of nonlinear distortion in the auditory system. Using harmonic and inharmonic "missing fundamental" complex tone stimuli, it is demonstrated that: (a) missing fundamental pitch is not represented as a spectral peak in the FFR, (b) the FFR contains energy at the stimulus envelope frequency, primary tone frequencies, and nonlinear distortion product frequencies, and (c) human pitch perception can be predicted by a weighted average of envelope-locked and phase-locked neural activity in the FFR. The origin and properties of nonlinear distortion products measured in the FFR are also investigated

An auditory neural correlate suggests a mechanism underlying holistic pitch perception.

Current theories of auditory pitch perception propose that cochlear place (spectral) and activity timing pattern (temporal) information are somehow combined within the brain to produce holistic pitch percepts, yet the neural mechanisms for integrating these two kinds of information remain obscure. To examine this process in more detail, stimuli made up of three pure tones whose components are individually resolved by the peripheral auditory system, but that nonetheless elicit a holistic, "missing fundamental" pitch percept, were played to human listeners. A technique was used to separate neural timing activity related to individual components of the tone complexes from timing activity related to an emergent feature of the complex (the envelope), and the region of the tonotopic map where information could originate from was simultaneously restricted by masking noise. Pitch percepts were mirrored to a very high degree by a simple combination of component-related and envelope-related neural responses with similar timing that originate within higher-frequency regions of the tonotopic map where stimulus components interact. These results suggest a coding scheme for holistic pitches whereby limited regions of the tonotopic map (spectral places) carrying envelope- and component-related activity with similar timing patterns selectively provide a key source of neural pitch information. A similar mechanism of integration between local and emergent object properties may contribute to holistic percepts in a variety of sensory systems

Figure 2

<p>Stimulus design and evoked potential responses. (a) Amplitude-time waveforms showing stimulus construction by adding band-passed, random phase noise (top, left) to repeating 3-note tone complexes (top, center) to produce the stimuli used in perceptual testing and for evoked-potential recording. There were five different tone complexes used; each is shown color-coded above its constituent components on an amplitude–frequency plot (bottom), where the components of each tone are overlaid on a common set of axes. (b,c) Amplitude spectra of the evoked potential responses from a single subject for two of the stimulus tones. The sum of the 0° and 180° responses is shown in black (envelope-related), and the difference of the 0° and 180° responses is shown in red or green (fine-structure phase-related). The y-axis is in units of relative amplitude; the corresponding measured values for the highest y-axis marker are 0.38 µV (black) and 0.35 µV (red) for Figure 2b, and 0.26 µV (black) and 0.23 µV (green) for Figure 2c. Colors refer to Figure 2a. (d,e) Mean relative amplitude spectra (n = 22 subjects) of peaks in the fine-structure-related (difference, Figure 2d) and envelope-related (sum, Figure 2e) evoked potential responses, all of which passed criteria for robustness (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000369#s4" target="_blank">Methods</a>). Responses to each stimulus tone have been overlaid on the same set of axes. Colors refer to Figure 2a. Error bars represent 95% confidence intervals around the mean value.</p

Importance of Maximal Strength and Muscle-Tendon Mechanics for Improving Force Steadiness in Persons with Parkinson’s Disease

Although plantar flexion force steadiness (FS) is reduced in persons with Parkinson’s disease (PD), the underlying causes are unknown. The aim of this exploratory design study was to ascertain the influence of maximal voluntary contraction (MVC) force and gastrocnemius-Achilles muscle-tendon unit behaviour on FS in persons with PD. Nine persons with PD and nine age- and sex-matched non-PD controls (~70 years, 6 females per group) performed plantar flexion MVCs and sub-maximal tracking tasks at 5, 10, 25, 50 and 75% MVC. Achilles tendon elongation and medial gastrocnemius fascicle lengths were recorded via ultrasound during contraction. FS was quantified using the coefficient of variation (CV) of force. Contributions of MVC and tendon mechanics to FS were determined using multiple regression analyses. Persons with PD were 35% weaker during MVC (p = 0.04) and had 97% greater CV (p = 0.01) with 47% less fascicle shortening (p = 0.004) and 38% less tendon elongation (p = 0.002) than controls. Reduced strength was a direct contributor to lower FS in PD (ß = 0.631), and an indirect factor through limiting optimal muscle-tendon unit interaction. Interestingly, our findings indicate an uncoupling between fascicle shortening and tendon elongation in persons with PD. To better understand limitations in FS and muscle-tendon unit behavior, it is imperative to identify the origins of MVC decrements in persons with PD.Health and Social Development, Faculty of (Okanagan)Non UBCHealth and Exercise Sciences, School of (Okanagan)ReviewedFacult

Investigation of serotonergic Parkinson's disease-related covariance pattern using [11C]-DASB/PET

We used positron emission tomography imaging with [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)- benzonitrile (DASB) and principal component analysis to investigate whether a specific Parkinson's disease (PD)-related spatial covariance pattern could be identified for the serotonergic system. We also explored if non-manifesting leucine-rich repeat kinase 2 (LRRK2) mutation carriers, with normal striatal dopaminergic innervation as measured with [11C]-dihydrotetrabenazine (DTBZ), exhibit a distinct spatial covariance pattern compared to healthy controls and subjects with manifest PD. 15 subjects with sporadic PD, eight subjects with LRRK2 mutation-associated PD, nine LRRK2 non-manifesting mutation carriers, and nine healthy controls participated in the study. The analysis was applied to the DASB non-displaceable binding potential values evaluated in 42 pre-defined regions of interest. PD was found to be associated with a specific spatial covariance pattern, comprising relatively decreased DASB binding in the caudate, putamen and substantia nigra and relatively preserved binding in the hypothalamus and hippocampus; the expression of this pattern in PD subjects was significantly higher than in healthy controls (P < 0.001) and correlated significantly with disease duration (P < 0.01) and with DTBZ binding in the more affected putamen (P < 0.01). The LRRK2 non-manifesting mutation carriers expressed a different pattern, also significantly different from healthy controls (P < 0.001), comprising relatively decreased DASB binding in the pons, pedunculopontine nucleus, thalamus and rostral raphe nucleus, and with relatively preserved binding in the hypothalamus, amygdala, hippocampus and substantia nigra. This pattern was not present in either sporadic or LRRK2 mutation-associated PD subjects. These findings, although obtained with a relatively limited number of subjects, suggest that specific and overall distinct spatial serotonergic patterns may be associated with PD and LRRK2 mutations. Alterations in regions where relative upregulation is observed in both patterns may be indicative of compensatory mechanisms preceding or protecting from disease manifestation

PBB3 Imaging in Parkinsonian disorders: evidence for binding to Tau and other proteins

Background and Objectives: To study selective regional binding for tau pathology in vivo, using PET with [11C]PBB3 in PSP patients, and other conditions not typically associated with tauopathy.\nMethods: Dynamic PET scans were obtained for 70 minutes after the bolus injection of [11C]PBB3 in 5 PSP subjects, 1 subject with DCTN1 mutation and PSP phenotype, 3 asymptomatic SNCA duplication carriers, 1 MSA subject, and 6 healthy controls of similar age. Tissue reference Logan analysis was applied to each region of interest using a cerebellar white matter reference region.\nResults: In comparison to the control group, PSP subjects showed specific uptake of [11C]PBB3 in putamen, midbrain, GP, and SN. Longer disease duration and more advanced clinical severity were generally associated with higher tracer retention. A DCTN1/PSP phenotype case showed increased binding in putamen, parietal lobe, and GP. In SNCA duplication carriers, there was a significant increase of [11C] PBB3 binding in GP, putamen, thalamus, ventral striatum, SN, and pedunculopontine nucleus. The MSA case showed increased binding in frontal lobe, GP, midbrain, parietal lobe, putamen, temporal lobe, SN, thalamus, and ventral striatum.\nConclusions: All PSP patients showed increased retention of the tracer in the basal ganglia, as expected. Binding was also present in asymptomatic SNCA duplication carriers and in an MSA case, which are not typically associated with pathological tau deposition. This suggests the possibility that [11C]PBB3 binds to alpha-synuclein. © 2017 International Parkinson and Movement Disorder Societ

PBB3 Imaging in Parkinsonian disorders: Evidence for binding to abnormally aggregated proteins in addition to tau proteins

Objective: To study selective regional binding for tau pathology in vivo, using PET with [11C]PBB3 ([11C]methylamino pyridin-3-yl buta-1,3-dienyl benzo[d]thiazol-6-ol) in tauopathies, and in conditions not typically associated with tauopathy. Background: Tau imaging is a promising tool to study the link between tau and neurodegeneration. The specificity of tracers in vivo however remains uncertain, and off target binding is frequently present, limiting its use in parkinsonian disorders. Methods: Dynamic PET scans were obtained for 70 min after the bolus injection of [11C]PBB3 (mean dose 518.97MBq) in five PSP subjects, 1 subject with DCTN1 mutation and PSP phenotype,3 asymptomatic SNCA duplication carriers, 1 MSA subject, and 7 healthy controls of similar age. The occipital cortex was used as reference region for the PSP , the DCTN1 mutation and the MSA subjects. The cerebellar white matter was used as a reference region for the SNCA duplication carriers. Tissue reference Logan analysis was applied to each region of interest (ROI) using the appropriate reference region. Results: In PSP subjects, the highest retention of [11C]PBB3 was observed in putamen, midbrain, globus pallidus and substantia nigra. Longer disease duration and more advanced clinical severity were generally associated with higher tracer retention. The DCTN1/PSP phenotype case showed increased binding in putamen, parietal lobe, and globus pallidus. In SNCA duplication carriers there was a significant increase of [11C] PBB3 binding compared to controls in globus pallidus, putamen, thalamus, ventral striatum, substantia nigra, and pedunculopontine nucleus. The MSA case showed increased binding in comparison to the control group in frontal lobe, globus pallidus, midbrain, parietal lobe, putamen, temporal lobe, substantia nigra, thalamus and ventral striatum. Conclusions: All PSP patients showed increased retention of the tracer in the basal ganglia, as clinically expected. However, binding was also present in asymptomatic SNCA duplication carriers as well as the subject with MSA, which are not typically associated with pathological tau deposition. This suggests the possibility that [11C]PBB3 binds to alpha-synuclein or other proteins involved in neurodegeneration