Functional sex differences in human primary auditory cortex.
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ABSTRACT:
SUBMITTER: Ruytjens L
PROVIDER: S-EPMC2100432 | biostudies-other | 2007 Dec
REPOSITORIES: biostudies-other
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Project description:BackgroundDiurnal rhythms in gene expression have been detected in the human brain. Previous studies found that males and females exhibit 24-hour rhythms in known circadian genes, with earlier peak expression in females. Whether there are sex differences in large-scale transcriptional rhythms in the cortex that align with observed sex differences in physiological and behavioral rhythms is currently unknown.MethodsDiurnal rhythmicity of gene expression was determined for males and females using RNA sequencing data from human postmortem dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Sex differences among rhythmic genes were determined using significance cutoffs, threshold-free analyses, and R2 difference. Phase concordance was assessed across the DLPFC and ACC for males and females. Pathway and transcription factor analyses were also conducted on significantly rhythmic genes.ResultsCanonical circadian genes had diurnal rhythms in both sexes with similar amplitude and phase. When analyses were expanded to the entire transcriptome, significant sex differences in transcriptional rhythms emerged. There were nearly twice as many rhythmic transcripts in the DLPFC in males and nearly 4 times as many rhythmic transcripts in the ACC in females. Results suggest a diurnal rhythm in synaptic transmission specific to the ACC in females (e.g., GABAergic [gamma-aminobutyric acidergic] and cholinergic neurotransmission). For males, there was phase concordance between the DLPFC and ACC, while phase asynchrony was found in females.ConclusionsThere are robust sex differences in molecular rhythms of genes in the DLPFC and ACC, providing potential mechanistic insights into how neurotransmission and synaptic function are modulated in a circadian-dependent and sex-specific manner.
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Project description:The layers of the neocortex each have a unique anatomical connectivity and functional role. Their exploration in the human brain, however, has been severely restricted by the limited spatial resolution of non-invasive measurement techniques. Here, we exploit the sensitivity and specificity of ultra-high field fMRI at 7 Tesla to investigate responses to natural sounds at deep, middle, and superficial cortical depths of the human auditory cortex. Specifically, we compare the performance of computational models that represent different hypotheses on sound processing inside and outside the primary auditory cortex (PAC). We observe that while BOLD responses in deep and middle PAC layers are equally well represented by a simple frequency model and a more complex spectrotemporal modulation model, responses in superficial PAC are better represented by the more complex model. This indicates an increase in processing complexity in superficial PAC, which remains present throughout cortical depths in the non-primary auditory cortex. These results suggest that a relevant transformation in sound processing takes place between the thalamo-recipient middle PAC layers and superficial PAC. This transformation may be a first computational step towards sound abstraction and perception, serving to form an increasingly more complex representation of the physical input.
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Project description:Perception can be highly dependent on stimulus context, but whether and how sensory areas encode the context remains uncertain. We used an ambiguous auditory stimulus - a tritone pair - to investigate the neural activity associated with a preceding contextual stimulus that strongly influenced the tritone pair's perception: either as an ascending or a descending step in pitch. We recorded single-unit responses from a population of auditory cortical cells in awake ferrets listening to the tritone pairs preceded by the contextual stimulus. We find that the responses adapt locally to the contextual stimulus, consistent with human MEG recordings from the auditory cortex under the same conditions. Decoding the population responses demonstrates that pitch-change selective cells are able to predict well the context-sensitive percept of the tritone pairs. Conversely, decoding the distances between the pitch representations predicts the opposite of the percept. The various percepts can be readily captured and explained by a neural model of cortical activity based on populations of adapting, pitch and pitch-direction selective cells, aligned with the neurophysiological responses. Together, these decoding and model results suggest that contextual influences on perception may well be already encoded at the level of the primary sensory cortices, reflecting basic neural response properties commonly found in these areas.
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Project description:Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used muscimol infusions in rats to show that discriminatory threat learning requires Au1 activity specifically during memory acquisition and retrieval, but not during consolidation. Memory specificity was similarly disrupted by infusion of PKMζ inhibitor peptide (ZIP) during memory storage. Our findings show that Au1 is required at critical memory phases and suggest that Au1 plasticity enables stimulus discrimination.
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Project description:BackgroundWhile human auditory cortex is known to contain tonotopically organized auditory cortical fields (ACFs), little is known about how processing in these fields is modulated by other acoustic features or by attention.Methodology/principal findingsWe used functional magnetic resonance imaging (fMRI) and population-based cortical surface analysis to characterize the tonotopic organization of human auditory cortex and analyze the influence of tone intensity, ear of delivery, scanner background noise, and intermodal selective attention on auditory cortex activations. Medial auditory cortex surrounding Heschl's gyrus showed large sensory (unattended) activations with two mirror-symmetric tonotopic fields similar to those observed in non-human primates. Sensory responses in medial regions had symmetrical distributions with respect to the left and right hemispheres, were enlarged for tones of increased intensity, and were enhanced when sparse image acquisition reduced scanner acoustic noise. Spatial distribution analysis suggested that changes in tone intensity shifted activation within isofrequency bands. Activations to monaural tones were enhanced over the hemisphere contralateral to stimulation, where they produced activations similar to those produced by binaural sounds. Lateral regions of auditory cortex showed small sensory responses that were larger in the right than left hemisphere, lacked tonotopic organization, and were uninfluenced by acoustic parameters. Sensory responses in both medial and lateral auditory cortex decreased in magnitude throughout stimulus blocks. Attention-related modulations (ARMs) were larger in lateral than medial regions of auditory cortex and appeared to arise primarily in belt and parabelt auditory fields. ARMs lacked tonotopic organization, were unaffected by acoustic parameters, and had distributions that were distinct from those of sensory responses. Unlike the gradual adaptation seen for sensory responses, ARMs increased in amplitude throughout stimulus blocks.Conclusions/significanceThe results are consistent with the view that medial regions of human auditory cortex contain tonotopically organized core and belt fields that map the basic acoustic features of sounds while surrounding higher-order parabelt regions are tuned to more abstract stimulus attributes. Intermodal selective attention enhances processing in neuronal populations that are partially distinct from those activated by unattended stimuli.
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Project description:Accumulating evidence shows that auditory cortex (AC) of humans, and other primates, is involved in more complex cognitive processes than feature segregation only, which are shaped by experience-dependent plasticity and thus likely show substantial individual variability. However, thus far, individual variability of ACs has been considered a methodological impediment rather than a phenomenon of theoretical importance. Here, we examined the variability of ACs using intrinsic functional connectivity patterns in humans and macaques. Our results demonstrate that in humans, interindividual variability is greater near the nonprimary than primary ACs, indicating that variability dramatically increases across the processing hierarchy. ACs are also more variable than comparable visual areas and show higher variability in the left than in the right hemisphere, which may be related to the left lateralization of auditory-related functions such as language. Intriguingly, remarkably similar modality differences and lateralization of variability were also observed in macaques. These connectivity-based findings are consistent with a confirmatory task-based functional magnetic resonance imaging analysis. The quantification of variability in auditory function, and the similar findings in both humans and macaques, will have strong implications for understanding the evolution of advanced auditory functions in humans.
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Project description:Recent research has demonstrated that resting-state functional connectivity (RS-FC) within the human auditory cortex (HAC) is frequency-selective, but whether RS-FC between the HAC and other brain areas is differentiated by frequency remains unclear. Three types of data were collected in this study, including resting-state functional magnetic resonance imaging (fMRI) data, task-based fMRI data using six pure tone stimuli (200, 400, 800, 1,600, 3,200, and 6,400 Hz), and structural imaging data. We first used task-based fMRI to identify frequency-selective cortical regions in the HAC. Six regions of interest (ROIs) were defined based on the responses of 50 participants to the six pure tone stimuli. Then, these ROIs were used as seeds to determine RS-FC between the HAC and other brain regions. The results showed that there was RS-FC between the HAC and brain regions that included the superior temporal gyrus, dorsolateral prefrontal cortex (DL-PFC), parietal cortex, occipital lobe, and subcortical structures. Importantly, significant differences in FC were observed among most of the brain regions that showed RS-FC with the HAC. Specifically, there was stronger RS-FC between (1) low-frequency (200 and 400 Hz) regions and brain regions including the premotor cortex, somatosensory/-association cortex, and DL-PFC; (2) intermediate-frequency (800 and 1,600 Hz) regions and brain regions including the anterior/posterior superior temporal sulcus, supramarginal gyrus, and inferior frontal cortex; (3) intermediate/low-frequency regions and vision-related regions; (4) high-frequency (3,200 and 6,400 Hz) regions and the anterior cingulate cortex or left DL-PFC. These findings demonstrate that RS-FC between the HAC and other brain areas is frequency selective.
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