Integration of auditory and visual communication information in the primate ventrolateral prefrontal cortex

The integration of auditory and visual stimuli is crucial for recognizing objects, communicating effectively, and navigating through our complex world. Although the frontal lobes are involved in memory, communication, and language, there has been no evidence that the integration of communication information occurs at the single-cell level in the frontal lobes. Here, we show that neurons in the macaque ventrolateral prefrontal cortex (VLPFC) integrate audiovisual communication stimuli. The multisensory interactions included both enhancement and suppression of a predominantly auditory or a predominantly visual response, although multisensory suppression was the more common mode of response. The multisensory neurons were distributed across the VLPFC and within previously identified unimodal auditory and visual regions (O’Scalaidhe et al., 1997; Romanski and Goldman-Rakic, 2002). Thus, our study demonstrates, for the first time, that single prefrontal neurons integrate communication information from the auditory and visual domains, suggesting that these neurons are an important node in the cortical network responsible for communication

The statistical neuroanatomy of frontal networks in the macaque

We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework

Audiovisual integration in macaque face patch neurons

Primate social communication depends on the perceptual integration of visual and auditory cues, reflected in the multimodal mixing of sensory signals in certain cortical areas. The macaque cortical face patch network, identified through visual, face-selective responses measured with fMRI, is assumed to contribute to visual social interactions. However, whether face patch neurons are also influenced by acoustic information, such as the auditory component of a natural vocalization, remains unknown. Here, we recorded single-unit activity in the anterior fundus (AF) face patch, in the superior temporal sulcus, and anterior medial (AM) face patch, on the undersurface of the temporal lobe, in macaques presented with audiovisual, visual-only, and auditory-only renditions of natural movies of macaques vocalizing. The results revealed that 76% of neurons in face patch AF were significantly influenced by the auditory component of the movie, most often through enhancement of visual responses but sometimes in response to the auditory stimulus alone. By contrast, few neurons in face patch AM exhibited significant auditory responses or modulation. Control experiments in AF used an animated macaque avatar to demonstrate, first, that the structural elements of the face were often essential for audiovisual modulation and, second, that the temporal modulation of the acoustic stimulus was more important than its frequency spectrum. Together, these results identify a striking contrast between two face patches and specifically identify AF as playing a potential role in the integration of audiovisual cues during natural modes of social communication

Response of the primary auditory and non-auditory cortices to acoustic stimulation: A manganese-enhanced MRI study

Structural and functional features of various cerebral cortices have been extensively explored in neuroscience research. We used manganese-enhanced MRI, a non-invasive method for examining stimulus-dependent activity in the whole brain, to investigate the activity in the layers of primary cortices and sensory, such as auditory and olfactory, pathways under acoustic stimulation. Male Sprague-Dawley rats, either with or without exposure to auditory stimulation, were scanned before and 24-29 hour after systemic MnCl2 injection. Cortex linearization and layer-dependent signal extraction were subsequently performed for detecting layer-specific cortical activity. We found stimulus-dependent activity in the deep layers of the primary auditory cortex and the auditory pathways. The primary sensory and visual cortices also showed the enhanced activity, whereas the olfactory pathways did not. Further, we performed correlation analysis of the signal intensity ratios among different layers of each cortex, and compared the strength of correlations between with and without the auditory stimulation. In the primary auditory cortex, the correlation strength between left and right hemisphere showed a slight but not significant increase with the acoustic simulation, whereas, in the primary sensory and visual cortex, the correlation coefficients were significantly smaller. These results suggest the possibility that even though the primary auditory, sensory, and visual cortices showed enhanced activity to the auditory stimulation, these cortices had different associations for auditory processing in the brain network.open0

Functional sex differences in human primary auditory cortex

Background We used PET to study cortical activation during auditory stimulation and found sex differences in the human primary auditory cortex (PAC). Regional cerebral blood flow (rCBF) was measured in 10 male and 10 female volunteers while listening to sounds (music or white noise) and during a baseline (no auditory stimulation). Results and discussion We found a sex difference in activation of the left and right PAC when comparing music to noise. The PAC was more activated by music than by noise in both men and women. But this difference between the two stimuli was significantly higher in men than in women. To investigate whether this difference could be attributed to either music or noise, we compared both stimuli with the baseline and revealed that noise gave a significantly higher activation in the female PAC than in the male PAC. Moreover, the male group showed a deactivation in the right prefrontal cortex when comparing noise to the baseline, which was not present in the female group. Interestingly, the auditory and prefrontal regions are anatomically and functionally linked and the prefrontal cortex is known to be engaged in auditory tasks that involve sustained or selective auditory attention. Thus we hypothesize that differences in attention result in a different deactivation of the right prefrontal cortex, which in turn modulates the activation of the PAC and thus explains the sex differences found in the activation of the PAC. Conclusion Our results suggest that sex is an important factor in auditory brain studies

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Human Auditory Cortical Activation during Self-Vocalization

During speaking, auditory feedback is used to adjust vocalizations. The brain systems mediating this integrative ability have been investigated using a wide range of experimental strategies. In this report we examined how vocalization alters speech-sound processing within auditory cortex by directly recording evoked responses to vocalizations and playback stimuli using intracranial electrodes implanted in neurosurgery patients. Several new findings resulted from these high-resolution invasive recordings in human subjects. Suppressive effects of vocalization were found to occur only within circumscribed areas of auditory cortex. In addition, at a smaller number of sites, the opposite pattern was seen; cortical responses were enhanced during vocalization. This increase in activity was reflected in high gamma power changes, but was not evident in the averaged evoked potential waveforms. These new findings support forward models for vocal control in which efference copies of premotor cortex activity modulate sub-regions of auditory cortex

Speech Cues Contribute to Audiovisual Spatial Integration

Speech is the most important form of human communication but ambient sounds and competing talkers often degrade its acoustics. Fortunately the brain can use visual information, especially its highly precise spatial information, to improve speech comprehension in noisy environments. Previous studies have demonstrated that audiovisual integration depends strongly on spatiotemporal factors. However, some integrative phenomena such as McGurk interference persist even with gross spatial disparities, suggesting that spatial alignment is not necessary for robust integration of audiovisual place-of-articulation cues. It is therefore unclear how speech-cues interact with audiovisual spatial integration mechanisms. Here, we combine two well established psychophysical phenomena, the McGurk effect and the ventriloquist's illusion, to explore this dependency. Our results demonstrate that conflicting spatial cues may not interfere with audiovisual integration of speech, but conflicting speech-cues can impede integration in space. This suggests a direct but asymmetrical influence between ventral ‘what’ and dorsal ‘where’ pathways

Prefrontal Cortex Lesions Impair Object-Spatial Integration

How and where object and spatial information are perceptually integrated in the brain is a central question in visual cognition. Single-unit physiology, scalp EEG, and fMRI research suggests that the prefrontal cortex (PFC) is a critical locus for object-spatial integration. To test the causal participation of the PFC in an object-spatial integration network, we studied ten patients with unilateral PFC damage performing a lateralized object-spatial integration task. Consistent with single-unit and neuroimaging studies, we found that PFC lesions result in a significant behavioral impairment in object-spatial integration. Furthermore, by manipulating inter-hemispheric transfer of object-spatial information, we found that masking of visual transfer impairs performance in the contralesional visual field in the PFC patients. Our results provide the first evidence that the PFC plays a key, causal role in an object-spatial integration network. Patient performance is also discussed within the context of compensation by the non-lesioned PFC