Forward entrainment: Psychophysics, neural correlates, and function.

We define forward entrainment as that part of behavioral or neural entrainment that outlasts the entraining stimulus. In this review, we examine conditions under which one may optimally observe forward entrainment. In Part 1, we review and evaluate studies that have observed forward entrainment using a variety of psychophysical methods (detection, discrimination, and reaction times), different target stimuli (tones, noise, and gaps), different entraining sequences (sinusoidal, rectangular, or sawtooth waveforms), a variety of physiological measures (MEG, EEG, ECoG, CSD), in different modalities (auditory and visual), across modalities (audiovisual and auditory-motor), and in different species. In Part 2, we describe those experimental conditions that place constraints on the magnitude of forward entrainment, including an evaluation of the effects of signal uncertainty and attention, temporal envelope complexity, signal-to-noise ratio (SNR), rhythmic rate, prior experience, and intersubject variability. In Part 3 we theorize on potential mechanisms and propose that forward entrainment may instantiate a dynamic auditory afterimage that lasts a fraction of a second to minimize prediction error in signal processing.

Informational Masking in Aging and Brain-lesioned Individuals.

Auditory stream segregation and informational masking were investigated in brain-lesioned individuals, age-matched controls with no neurological disease, and young college-age students. A psychophysical paradigm known as rhythmic masking release (RMR) was used to examine the ability of participants to identify a change in the rhythmic sequence of 20-ms Gaussian noise bursts presented through headphones and filtered through generalized head-related transfer functions to produce the percept of an externalized auditory image (i.e., a 3D virtual reality sound). The target rhythm was temporally interleaved with a masker sequence comprising similar noise bursts in a manner that resulted in a uniform sequence with no information remaining about the target rhythm when the target and masker were presented from the same location (an impossible task). Spatially separating the target and masker sequences allowed participants to determine if there was a change in the target rhythm midway during its presentation. RMR thresholds were defined as the minimum spatial separation between target and masker sequences that resulted in 70.7% correct-performance level in a single-interval 2-alternative forced-choice adaptive tracking procedure. The main findings were (1) significantly higher RMR thresholds for individuals with brain lesions (especially those with damage to parietal areas) and (2) a left-right spatial asymmetry in performance for lesion (but not control) participants. These findings contribute to a better understanding of spatiotemporal relations in informational masking and the neural bases of auditory scene analysis.

Detection of dynamic changes in interaural delay by older adults (L).

The ability of older adults (48 to 72) with relatively intact low-frequency hearing to detect the motion of an acoustic source was investigated using dynamically varying interaural delays. Thresholds were measured using a single-interval two-alternative forced-choice task in which listeners determined if the sound source was moving or stationary. Motion thresholds were significantly larger than stationary localization thresholds. No correlation was observed between age and motion-detection ability for the age range tested. An interesting finding was that there were similar thresholds for older and younger adults. Results suggest reliance on dominant low-frequency binaural timing cues unaffected by high-frequency hearing loss in older adults.

Confirming an antiphasic bicyclic pattern of forward entrainment in signal detection: A reanalysis of Sun et al. (2021).

Forward entrainment refers to that part of the entrainment process that persists after termination of an entraining stimulus. Hickok et al. (2015) reported forward entrainment in signal detection that lasted for two post-stimulus cycles. In a recent paper, Sun et al. (2021) reported new data which suggested an absence of entrainment effects (Eur. J. Neurosci, 1-18, doi.org/10.1111/ejn.15367). Here we show that when Sun et al.'s data are analysed using unbiased detection-theoretic measures, a clear antiphasic bicyclic pattern of entrainment is observed. We further show that the measure of entrainment strength used by Sun et al., the normalized Fourier transform of performance curves, is not only erroneously calculated but is also unreliable in estimating entrainment strength due to signal-processing artifacts.

A critical analysis of Lin et al.'s (2021) failure to observe forward entrainment in pitch discrimination.

Forward entrainment refers to that part of the entrainment process that outlasts the entraining stimulus. Several studies have demonstrated psychophysical forward entrainment in a pitch-discrimination task. In a recent paper, Lin et al. (2021) challenged these findings by demonstrating that a sequence of 4 entraining pure tones does not affect the ability to determine whether a frequency modulated pulse, presented after termination of the entraining sequence, has swept up or down in frequency. They concluded that rhythmic sequences do not facilitate pitch discrimination. Here, we describe several methodological and stimulus design flaws in Lin et al.'s study that may explain their failure to observe forward entrainment in pitch discrimination.

The rhythm of attention: Perceptual modulation via rhythmic entrainment is lowpass and attention mediated.

Modulation patterns are known to carry critical predictive cues to signal detection in complex acoustic environments. The current study investigated the persistence of masker modulation effects on postmodulation detection of probe signals. Hickok, Farahbod, and Saberi (Psychological Science, 26, 1006-1013, 2015) demonstrated that thresholds for a tone pulse in stationary noise follow a predictable periodic pattern when preceded by a 3-Hz amplitude modulated masker. They found entrainment of detection patterns to the modulation envelope lasting for approximately two cycles after termination of modulation. The current study extends these results to a wide range of modulation rates by mapping the temporal modulation transfer function for persistent modulatory effects. We found significant entrainment to modulation rates of 2 and 3 Hz, a weaker effect at 5 Hz, and no entrainment at higher rates (8 to 32 Hz). The effect seems critically dependent on attentional mechanisms, requiring temporal and level uncertainty of the probe signal. Our findings suggest that the persistence of modulatory effects on signal detection is lowpass in nature and attention based.

The Effect of Topical Vitamin A and E on Ischemic Random Skin Flap Survival.

BACKGROUND: Ischemia of skin flaps is an important complication in reconstructive surgery. This study evaluated the efficacy of topical vitamins A and E on improving flap survival. METHODS: Twenty-four white-albino male rats were randomly divided into two groups of treatment and control. Standard rectangular, distally based dorsal random pattern skin flap was elevated. Intra-peritoneal cephazoline was administered to prevent any unexpected infection. No pharmaceutical agent was administered for the control group, but pure vaseline ointment. In treatment group, vaseline plus vitamins A and E were administrated daily after surgery for 10 days. The rats were evaluated on the 10th day after surgery for viable and necrotic portions of the flaps. RESULTS: The mean values of necrosis in the flaps were 625±189.56 and 920.00±247.31 in the treatment and control groups, respectively. Vaseline plus vitamins increased flap survival significantly. CONCLUSION: Topical vitamins A and E may be effective pharmaceutical agents to increase viability of random skin flaps in rats. They can be added to vasoactive topical agents to reach better results.

Robustness of speech intelligibility at moderate levels of spectral degradation.

The current study investigated how amplitude and phase information differentially contribute to speech intelligibility. Listeners performed a word-identification task after hearing spectrally degraded sentences. Each stimulus was degraded by first dividing it into segments, then the amplitude and phase components of each segment were decorrelated independently to various degrees relative to those of the original segment. Segments were then concatenated into their original sequence to present to the listener. We used three segment lengths: 30 ms (phoneme length), 250 ms (syllable length), and full sentence (non-segmented). We found that for intermediate spectral correlation values, segment length is generally inconsequential to intelligibility. Overall, intelligibility was more adversely affected by phase-spectrum decorrelation than by amplitude-spectrum decorrelation. If the phase information was left intact, decorrelating the amplitude spectrum to intermediate values had no effect on intelligibility. If the amplitude information was left intact, decorrelating the phase spectrum to intermediate values significantly degraded intelligibility. Some exceptions to this rule are described. These results delineate the range of amplitude- and phase-spectrum correlations necessary for speech processing and its dependency on the temporal window of analysis (phoneme or syllable length). Results further point to the robustness of speech information in environments that acoustically degrade cues to intelligibility (e.g., reverberant or noisy environments).

Auditory, Visual and Audiovisual Speech Processing Streams in Superior Temporal Sulcus.

The human superior temporal sulcus (STS) is responsive to visual and auditory information, including sounds and facial cues during speech recognition. We investigated the functional organization of STS with respect to modality-specific and multimodal speech representations. Twenty younger adult participants were instructed to perform an oddball detection task and were presented with auditory, visual, and audiovisual speech stimuli, as well as auditory and visual nonspeech control stimuli in a block fMRI design. Consistent with a hypothesized anterior-posterior processing gradient in STS, auditory, visual and audiovisual stimuli produced the largest BOLD effects in anterior, posterior and middle STS (mSTS), respectively, based on whole-brain, linear mixed effects and principal component analyses. Notably, the mSTS exhibited preferential responses to multisensory stimulation, as well as speech compared to nonspeech. Within the mid-posterior and mSTS regions, response preferences changed gradually from visual, to multisensory, to auditory moving posterior to anterior. Post hoc analysis of visual regions in the posterior STS revealed that a single subregion bordering the mSTS was insensitive to differences in low-level motion kinematics yet distinguished between visual speech and nonspeech based on multi-voxel activation patterns. These results suggest that auditory and visual speech representations are elaborated gradually within anterior and posterior processing streams, respectively, and may be integrated within the mSTS, which is sensitive to more abstract speech information within and across presentation modalities. The spatial organization of STS is consistent with processing streams that are hypothesized to synthesize perceptual speech representations from sensory signals that provide convergent information from visual and auditory modalities.

Velocity Selective Networks in Human Cortex Reveal Two Functionally Distinct Auditory Motion Systems.

The auditory system encounters motion cues through an acoustic object's movement or rotation of the listener's head in a stationary sound field, generating a wide range of naturally occurring velocities from a few to several hundred degrees per second. The angular velocity of moving acoustic objects relative to a listener is typically slow and does not exceed tens of degrees per second, whereas head rotations in a stationary acoustic field may generate fast-changing spatial cues in the order of several hundred degrees per second. We hypothesized that these two types of systems (i.e., encoding slow movements of an object or fast head rotations) may engage functionally distinct substrates in processing spatially dynamic auditory cues, with the latter potentially involved in maintaining perceptual constancy in a stationary field during head rotations and therefore possibly involving corollary-discharge mechanisms in premotor cortex. Using fMRI, we examined cortical response patterns to sound sources moving at a wide range of velocities in 3D virtual auditory space. We found a significant categorical difference between fast and slow moving sounds, with stronger activations in response to higher velocities in the posterior superior temporal regions, the planum temporale, and notably the premotor ventral-rostral (PMVr) area implicated in planning neck and head motor functions.

Imperfect pitch: Gabor's uncertainty principle and the pitch of extremely brief sounds.

How brief must a sound be before its pitch is no longer perceived? The uncertainty tradeoff between temporal and spectral resolution (Gabor's principle) limits the minimum duration required for accurate pitch identification or discrimination. Prior studies have reported that pitch can be extracted from sinusoidal pulses as brief as half a cycle. This finding has been used in a number of classic papers to develop models of pitch encoding. We have found that phase randomization, which eliminates timbre confounds, degrades this ability to chance, raising serious concerns over the foundation on which classic pitch models have been built. The current study investigated whether subthreshold pitch cues may still exist in partial-cycle pulses revealed through statistical integration in a time series containing multiple pulses. To this end, we measured frequency-discrimination thresholds in a two-interval forced-choice task for trains of partial-cycle random-phase tone pulses. We found that residual pitch cues exist in these pulses but discriminating them requires an order of magnitude (ten times) larger frequency difference than that reported previously, necessitating a re-evaluation of pitch models built on earlier findings. We also found that as pulse duration is decreased to less than two cycles its pitch becomes biased toward higher frequencies, consistent with predictions of an auto-correlation model of pitch extraction.

Enhanced tethered-flight duration and locomotor activity by overexpression of the human gene SOD1 in Drosophila motorneurons.

Mutation of the human gene superoxide dismutase (hSOD1) is associated with the fatal neurodegenerative disease familial amyotrophic lateral sclerosis (Lou Gehrig's disease). Selective overexpression of hSOD1 in Drosophila motorneurons increases lifespan to 140% of normal. The current study was designed to determine resistance to lifespan decline and failure of sensorimotor functions by overexpressing hSOD1 in Drosophila's motorneurons. First, we measured the ability to maintain continuous flight and wingbeat frequency (WBF) as a function of age (5 to 50 days). Flies overexpressing hSOD1 under the D42-GAL4 activator were able to sustain flight significantly longer than controls, with the largest effect observed in the middle stages of life. The hSOD1-expressed line also had, on average, slower wingbeat frequencies in late, but not early life relative to age-matched controls. Second, we examined locomotor (exploratory walking) behavior in late life when flies had lost the ability to fly (age ≥ 60 d). hSOD1-expressed flies showed significantly more robust walking activity relative to controls. Findings show patterns of functional decline dissimilar to those reported for other life-extended lines, and suggest that the hSOD1 gene not only delays death but enhances sensorimotor abilities critical to survival even in late life.

The Rhythm of Perception: Entrainment to Acoustic Rhythms Induces Subsequent Perceptual Oscillation.

Acoustic rhythms are pervasive in speech, music, and environmental sounds. Recent evidence for neural codes representing periodic information suggests that they may be a neural basis for the ability to detect rhythm. Further, rhythmic information has been found to modulate auditory-system excitability, which provides a potential mechanism for parsing the acoustic stream. Here, we explored the effects of a rhythmic stimulus on subsequent auditory perception. We found that a low-frequency (3 Hz), amplitude-modulated signal induces a subsequent oscillation of the perceptual detectability of a brief nonperiodic acoustic stimulus (1-kHz tone); the frequency but not the phase of the perceptual oscillation matches the entrained stimulus-driven rhythmic oscillation. This provides evidence that rhythmic contexts have a direct influence on subsequent auditory perception of discrete acoustic events. Rhythm coding is likely a fundamental feature of auditory-system design that predates the development of explicit human enjoyment of rhythm in music or poetry.

Improved functional abilities of the life-extended Drosophila mutant Methuselah are reversed at old age to below control levels.

Methuselah (mth) is a chromosome 3 Drosophila mutant with an increased lifespan. A large number of studies have investigated the genetic, molecular, and biochemical mechanisms of the mth gene. Much less is known about the effects of mth on preservation of sensorimotor abilities throughout Drosophila's lifespan, particularly in late life. The current study investigated functional senescence in mth and its parental-control line (w1118) in two experiments that measured age-dependent changes in flight functions and locomotor activity. In experiment 1, a total of 158 flies (81 mth and 77 controls) with an age range from 10 to 70 days were individually tethered under an infrared laser-sensor system that allowed monitoring of flight duration during phototaxic flight. We found that mth has a statistically significant advantage in maintaining continuous flight over control flies at age 10 days, but not during middle and late life. At age 70 days, the trend reversed and parental control flies had a small but significant advantage, suggesting an interaction between age and genotype in the ability to sustain flight. In experiment 2, a total of 173 different flies (97 mth and 76 controls) with an age range from 50 to 76 days were individually placed in a large well-lit arena (60 × 45 cm) and their locomotor activity quantified as the distance walked in a 1-min period. Results showed that mth flies had lower levels of locomotor activity relative to controls at ages 50 and 60 days. These levels converged for the two genotypes at the oldest ages tested. Findings show markedly different patterns of functional decline for the mth line relative to those previously reported for other life-extended genotypes, suggesting that different life-extending genes have dissimilar effects on preservation of sensory and motor abilities throughout an organism's lifespan.

An fMRI Study of Audiovisual Speech Perception Reveals Multisensory Interactions in Auditory Cortex.

Research on the neural basis of speech-reading implicates a network of auditory language regions involving inferior frontal cortex, premotor cortex and sites along superior temporal cortex. In audiovisual speech studies, neural activity is consistently reported in posterior superior temporal Sulcus (pSTS) and this site has been implicated in multimodal integration. Traditionally, multisensory interactions are considered high-level processing that engages heteromodal association cortices (such as STS). Recent work, however, challenges this notion and suggests that multisensory interactions may occur in low-level unimodal sensory cortices. While previous audiovisual speech studies demonstrate that high-level multisensory interactions occur in pSTS, what remains unclear is how early in the processing hierarchy these multisensory interactions may occur. The goal of the present fMRI experiment is to investigate how visual speech can influence activity in auditory cortex above and beyond its response to auditory speech. In an audiovisual speech experiment, subjects were presented with auditory speech with and without congruent visual input. Holding the auditory stimulus constant across the experiment, we investigated how the addition of visual speech influences activity in auditory cortex. We demonstrate that congruent visual speech increases the activity in auditory cortex.

Enhanced optomotor efficiency by expression of the human gene superoxide dismutase primarily in Drosophila motorneurons.

Mutation of the human gene superoxide dismutase (hSOD1) triggers the fatal neurodegenerative motorneuron disorder, familial amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). Broad expression of this gene in Drosophila has no effect on longevity or functional senescence. We show here that restricting expression of human SOD1 primarily to motorneurons of Drosophila has significant effects on optomotor efficiency during in-flight tracking of rapidly moving visual targets. Under high-stress workloads with a recursive visual-motion stimulus cycle, young isogenic controls failed to track rapidly changing visual cues, whereas their same-aged hSOD1-activated progeny maintained coordinated in-flight tracking of the target by phase locking to the dynamic visual movement patterns. Several explanations are considered for the observed effects, including antioxidant intervention in motorneurons, changes in signal transduction pathways that regulate patterns of gene expression in other cell types, and expression of hSOD1 in a small set of neurons in the central brain. That hSOD1 overexpression improves sensorimotor coordination in young organisms may suggest possible therapeutic strategies for early-onset ALS in humans.

Orthogonal acoustic dimensions define auditory field maps in human cortex.

The functional organization of human auditory cortex has not yet been characterized beyond a rudimentary level of detail. Here, we use functional MRI to measure the microstructure of orthogonal tonotopic and periodotopic gradients forming complete auditory field maps (AFMs) in human core and belt auditory cortex. These AFMs show clear homologies to subfields of auditory cortex identified in nonhuman primates and in human cytoarchitectural studies. In addition, we present measurements of the macrostructural organization of these AFMs into "clover leaf" clusters, consistent with the macrostructural organization seen across human visual cortex. As auditory cortex is at the interface between peripheral hearing and central processes, improved understanding of the organization of this system could open the door to a better understanding of the transformation from auditory spectrotemporal signals to higher-order information such as speech categories.

Response Bias Modulates the Speech Motor System during Syllable Discrimination.

Recent evidence suggests that the speech motor system may play a significant role in speech perception. Repetitive transcranial magnetic stimulation (TMS) applied to a speech region of premotor cortex impaired syllable identification, while stimulation of motor areas for different articulators selectively facilitated identification of phonemes relying on those articulators. However, in these experiments performance was not corrected for response bias. It is not currently known how response bias modulates activity in these networks. The present functional magnetic resonance imaging experiment was designed to produce specific, measureable changes in response bias in a speech perception task. Minimal consonant-vowel stimulus pairs were presented between volume acquisitions for same-different discrimination. Speech stimuli were embedded in Gaussian noise at the psychophysically determined threshold level. We manipulated bias by changing the ratio of same-to-different trials: 1:3, 1:2, 1:1, 2:1, 3:1. Ratios were blocked by run and subjects were cued to the upcoming ratio at the beginning of each run. The stimuli were physically identical across runs. Response bias (criterion, C) was measured in individual subjects for each ratio condition. Group mean bias varied in the expected direction. We predicted that activation in frontal but not temporal brain regions would co-vary with bias. Group-level regression of bias scores on percent signal change revealed a fronto-parietal network of motor and sensory-motor brain regions that were sensitive to changes in response bias. We identified several pre- and post-central clusters in the left hemisphere that overlap well with TMS targets from the aforementioned studies. Importantly, activity in these regions covaried with response bias even while the perceptual targets remained constant. Thus, previous results suggesting that speech motor cortex participates directly in the perceptual analysis of speech should be called into question.

FM-selective networks in human auditory cortex revealed using fMRI and multivariate pattern classification.

Frequency modulation (FM) is an acoustic feature of nearly all complex sounds. Directional FM sweeps are especially pervasive in speech, music, animal vocalizations, and other natural sounds. Although the existence of FM-selective cells in the auditory cortex of animals has been documented, evidence in humans remains equivocal. Here we used multivariate pattern analysis to identify cortical selectivity for direction of a multitone FM sweep. This method distinguishes one pattern of neural activity from another within the same ROI, even when overall level of activity is similar, allowing for direct identification of FM-specialized networks. Standard contrast analysis showed that despite robust activity in auditory cortex, no clusters of activity were associated with up versus down sweeps. Multivariate pattern analysis classification, however, identified two brain regions as selective for FM direction, the right primary auditory cortex on the supratemporal plane and the left anterior region of the superior temporal gyrus. These findings are the first to directly demonstrate existence of FM direction selectivity in the human auditory cortex.

Functionally distinct regions for spatial processing and sensory motor integration in the planum temporale.

There has been much debate recently over the functional role played by the planum temporale (PT) within the context of the dorsal auditory processing stream. Some studies indicate that regions in the PT support spatial hearing and other auditory functions, whereas others demonstrate sensory-motor response properties. This multifunctionality has led to the claim that the PT is performing a common computational pattern matching operation, then routing the signals (spatial, object, sensory-motor) into an appropriate processing stream. An alternative possibility is that the PT is functionally subdivided with separate regions supporting various functions. We assess this possibility using a within subject fMRI block design. DTI data were also collected to examine connectivity. There were four auditory conditions: stationary noise, moving noise, listening to pseudowords, and shadowing pseudowords (covert repetition). Contrasting the shadow and listen conditions should activate regions specific to sensory-motor processes, while contrasting the stationary and moving noise conditions should activate regions involved in spatial hearing. Subjects (N = 16) showed greater activation for shadowing in left posterior PT, area Spt, when the shadow and listen conditions were contrasted. The motion vs. stationary noise contrast revealed greater activation in a more medial and anterior portion of left PT. Seeds from these two contrasts were then used to guide the DTI analysis in an examination of connectivity via streamline tractography, which revealed different patterns of connectivity. Findings support a heterogeneous model of the PT, with functionally distinct regions for sensory-motor integration and processes involved in auditory spatial perception.