Michael W. Weiss

Dynamics of drug distribution. I. Role of the second and third curve moments

Conventionally, the dynamics of distribution in the body is evaluated by the so-called distribution half-life (e.g., t1/2,α but then the mean time of the distribution process is underestimated due tothe influence of elimination. By contrast, information about the dynamics of distribution contained in drug disposition curves can be extracted by the second and third curve moments, parameters that are related to the variance (VDRT)and skewness (SDRT)of residence time distributions; whereas the equilibrium state characterized by the volume of distribution (Vss), isdetermined by the mean residence time (MDRT)or the first curve moment. The approach represents a general noncompartmental analysis that is independent of a detailed structural model or a particular disposition function. Two parameters are introduced to characterize the dynamics of drug distribution: (i)the degree of departure of the system from “well-mixed” behavior of instantaneous distribution equilibrium (related to VDRT)and (ii)the mean time until equilibration is achieved (mean equilibration time, MEQT),which additionally depends on SDRT.Both parameters are quantitative measures of the dynamics of distribution and display explicit physical significance in terms of distribution within the corresponding noneliminating system. It is further shown that the so-called “distribution phase” in biexponential disposition curves is related to a monoexponential mixing curve of its corresponding noneliminating system with an equilibration or mixing half-time, t1/2,M=t1/2,α(Vβ/Vss*), where Vss*denotes the distribution volume of the noneliminating system. The results are applied to mixing and disposition curves measured for acetaminophen in liver-ligated and intact rats, respectively.

Something in the Way She Sings Enhanced Memory for Vocal Melodies

Across species, there is considerable evidence of preferential processing for biologically significant signals such as conspecific vocalizations and the calls of individual conspecifics. Surprisingly, music cognition in human listeners is typically studied with stimuli that are relatively low in biological significance, such as instrumental sounds. The present study explored the possibility that melodies might be remembered better when presented vocally rather than instrumentally. Adults listened to unfamiliar folk melodies, with some presented in familiar timbres (voice and piano) and others in less familiar timbres (banjo and marimba). They were subsequently tested on recognition of previously heard melodies intermixed with novel melodies. Melodies presented vocally were remembered better than those presented instrumentally even though they were liked less. Factors underlying the advantage for vocal melodies remain to be determined. In line with its biological significance, vocal music may evoke increased vigilance or arousal, which in turn may result in greater depth of processing and enhanced memory for musical details.

Enhanced Processing of Vocal Melodies in Childhood

Music cognition is typically studied with instrumental stimuli. Adults remember melodies better, however, when they are presented in a biologically significant timbre (i.e., the human voice) than in various instrumental timbres (Weiss, Trehub, & Schellenberg, 2012). We examined the impact of vocal timbre on childrens processing of melodies. In Study 1, 9- to 11-year-olds listened to 16 unfamiliar folk melodies (4 each of voice, piano, banjo, or marimba). They subsequently listened to the same melodies and 16 timbre-matched foils, and judged whether each melody was old or new. Vocal melodies were recognized better than instrumental melodies, which did not differ from one another, and the vocal advantage was consistent across age. In Study 2, 5- to 6-year-olds and 7- to 8-year-olds were tested with a simplified design that included only vocal and piano melodies. Both age groups successfully differentiated old from new melodies, but memory was more accurate for the older group. The older children recognized vocal melodies better than piano melodies, whereas the younger children tended to label vocal melodies as old whether they were old or new. The results provide the first evidence of differential processing of vocal and instrumental melodies in childhood.

Pianists exhibit enhanced memory for vocal melodies but not piano melodies.

Nonmusicians remember vocal melodies (i.e., sung to la la) better than instrumental melodies. If greater exposure to the voice contributes to those effects, then long-term experience with instrumental timbres should elicit instrument-specific advantages. Here we evaluate this hypothesis by comparing pianists with other musicians and nonmusicians. We also evaluate the possibility that absolute pitch (AP), which involves exceptional memory for isolated pitches, influences melodic memory. Participants heard 24 melodies played in four timbres (voice, piano, banjo, marimba) and were subsequently required to distinguish the melodies heard previously from 24 novel melodies presented in the same timbres. Musicians performed better than nonmusicians, but both groups showed a comparable memory advantage for vocal melodies. Moreover, pianists performed no better on melodies played on piano than on other instruments, and AP musicians performed no differently than non-AP musicians. The findings confirm the robust nature of the voice advantage and rule out explanations based on familiarity, practice, and motor representations.

Pupils dilate for vocal or familiar music.

Previous research reveals that vocal melodies are remembered better than instrumental renditions. Here we explored the possibility that the voice, as a highly salient stimulus, elicits greater arousal than nonvocal stimuli, resulting in greater pupil dilation for vocal than for instrumental melodies. We also explored the possibility that pupil dilation indexes memory for melodies. We tracked pupil dilation during a single exposure to 24 unfamiliar folk melodies (half sung to la la, half piano) and during a subsequent recognition test in which the previously heard melodies were intermixed with 24 novel melodies (half sung, half piano) from the same corpus. Pupil dilation was greater for vocal melodies than for piano melodies in the exposure phase and in the test phase. It was also greater for previously heard melodies than for novel melodies. Our findings provide the first evidence that pupillometry can be used to measure recognition of stimuli that unfold over several seconds. They also provide the first evidence of enhanced arousal to vocal melodies during encoding and retrieval, thereby supporting the more general notion of the voice as a privileged signal. (PsycINFO Database Record

Memory for melody and key in childhood

After only two exposures to previously unfamiliar melodies, adults remember the tunes for over a week and the key for over a day. Here, we examined the development of long-term memory for melody and key. Listeners in three age groups (7- to 8-year-olds, 9- to 11-year-olds, and adults) heard two presentations of each of 12 unfamiliar melodies. After a 10-min delay, they heard the same 12 old melodies intermixed with 12 new melodies. Half of the old melodies were transposed up or down by six semitones from initial exposure. Listeners rated how well they recognized the melodies from the exposure phase. Recognition was better for old than for new melodies, for adults compared to children, and for older compared to younger children. Recognition ratings were also higher for old melodies presented in the same key at test as exposure, and the detrimental effect of the transposition affected all age groups similarly. Although memory for melody improves with age and exposure to music, implicit memory for key appears to be adult-like by 7 years of age.