16 research outputs found

    fMRI Evidence for a Cortical Hierarchy of Pitch Pattern Processing

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    Pitch patterns, such as melodies, consist of two levels of structure: a global level, comprising the pattern of ups and downs, or contour; and a local level, comprising the precise intervals that make up this contour. An influential neuropsychological model suggests that these two levels of processing are hierarchically linked, with processing of the global structure occurring within the right hemisphere in advance of local processing within the left. However, the predictions of this model and its anatomical basis have not been tested in neurologically normal individuals. The present study used fMRI and required participants to listen to consecutive pitch sequences while performing a same/different one-back task. Sequences, when different, either preserved (local) or violated (global) the contour of the sequence preceding them. When the activations for the local and global conditions were contrasted directly, additional activation was seen for local processing in right planum temporale and posterior superior temporal sulcus (pSTS). The presence of additional activation for local over global processing supports the hierarchical view that the global structure of a pitch sequence acts as a “framework” on which the local detail is subsequently hung. However, the lateralisation of activation seen in the present study, with global processing occurring in left pSTS and local processing occurring bilaterally, differed from that predicted by the neuroanatomical model. A re-examination of the individual lesion data on which the neuroanatomical model is based revealed that the lesion data equally well support the laterality scheme suggested by our data. While the present study supports the hierarchical view of local and global processing, there is an evident need for further research, both in patients and neurologically normal individuals, before an understanding of the functional lateralisation of local and global processing can be considered established

    International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

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    Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

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    BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

    Congenital amusia : a short-term memory deficit for non-verbal, but not verbal sounds

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    Congenital amusia refers to a lifelong disorder of music processing and is linked to pitch-processing deficits. The present study investigated congenital amusics' short-term memory for tones, musical timbres and words. Sequences of five events (tones, timbres or words) were presented in pairs and participants had to indicate whether the sequences were the same or different. The performance of congenital amusics confirmed a memory deficit for tone sequences, but showed normal performance for word sequences. For timbre sequences, amusics' memory performance was impaired in comparison to matched controls. Overall timbre performance was found to be correlated with melodic contour processing (as assessed by the Montreal Battery of Evaluation of Amusia). The present findings show that amusics' deficits extend to non-verbal sound material other than pitch, in this case timbre, while not affecting memory for verbal material. This is in line with previous suggestions about the domain-specificity of congenital amusia

    Cross-modal facilitation in speech prosody.

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    International audienceSpeech prosody has traditionally been considered solely in terms of its auditory features, yet correlated visual features exist, such as head and eyebrow movements. This study investigated the extent to which visual prosodic features are able to affect the perception of the auditory features. Participants were presented with videos of a speaker pronouncing two words, with visual features of emphasis on one of these words. For each trial, participants saw one video where the two words were identical in both pitch and amplitude, and another video where there was a difference in either pitch or amplitude that was congruent or incongruent with the visual changes. Participants were asked to decide which video contained the sound difference. Thresholds were obtained for the congruent and incongruent videos, and for an auditory-alone condition. It was found that the congruent thresholds were better than the incongruent thresholds for both pitch and amplitude changes. Interestingly, the congruent thresholds for amplitude were better than for the auditory-alone condition, which implies that the visual features improve sensitivity to loudness changes. These results demonstrate that visual stimuli can affect auditory thresholds for changes in pitch and amplitude, and furthermore support the view that visual prosodic features enhance speech processing

    Effects of attention and unilateral neglect on auditory stream segregation

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    Two pairs of experiments studied the effects of attention and of unilateral neglect on auditory streaming. The first pair showed that the build up of auditory streaming in normal participants is gready reduced or absent when they attend to a competing task in the contralateral ear. It was concluded that the effective build up of streaming depends on attention. The second pair showed that patients with an attentional deficit toward the left side of space (unilateral neglect) show less stream segregation of tone sequences presented to their left than to their right ears. Streaming in their right ears was similar to that for stimuli presented to either ear of healthy and of brain-damaged controls, who showed no across-ear asymmetry. This result is consistent with an effect of attention on streaming, constrains the neural sites involved, and reveals a qualitative difference between the perception of left- and right-sided sounds by neglect patients. Auditory streaming is an example of the grouping or binding processes that have been extensively studied both in the auditory (e.g., Bregman, 1990; Darwin & Carlyon, 1995) and visual (e.g., Treisman & Gormican, 1988) domains. It is well-illustrated by the stimulus shown in Figure 1 (van Noorden, 1975), in which a pai

    Speech intonation perception deficits in musical tone deafness (congenital amusia)

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    International audienceTo what extent do music and language share neural mechanisms for processing pitch patterns? Musical tone-deafness (amusia) provides important evidence on this question. Amusics have problems with musical melody perception, yet early work suggested that they had no problems with the perception of speech intonation (Ayotte, Peretz, & Hyde, 2002). However, here we show that about 30% of amusics from independent studies (British and French-Canadian) have difficulty discriminating a statement from a question on the basis of a final pitch fall or rise.This suggests that pitch direction perception deficits in amusia (known from previous psychophysical work) can extend to speech. For British amusics, the direction deficit is related to the rate of change of the final pitch glide in statements/ questions, with increased discrimination difficulty when rates are relatively slow. These findings suggest that amusia provides a useful window on the neural relations between melodic processing in language and music

    The neural bases underlying pitch processing difficulties.

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    International audienceNormal listeners are often surprisingly poor at processing pitch changes. The neural bases of this difficulty were explored using magnetoencephalography (MEG) by comparing participants who obtained poor thresholds on a pitch-direction task with those who obtained good thresholds. Source-space projected data revealed that during an active listening task, the poor threshold group displayed greater activity in the left auditory cortical region when determining the direction of small pitch glides, whereas there was no difference in the good threshold group. In a passive listening task, a mismatch response (MMNm) was identified for pitch-glide direction deviants, with a tendency to be smaller in the poor listeners. The results imply that the difficulties in pitch processing are already apparent during automatic sound processing, and furthermore suggest that left hemisphere auditory regions are used by these listeners to consciously determine the direction of a pitch change. This is in line with evidence that the left hemisphere has a poor frequency resolution, and implies that normal listeners may use the sub-optimal hemisphere to process pitch changes
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