Plis de passage in the superior temporal sulcus: Morphology and local connectivity.

While there is a profusion of functional investigations involving the superior temporal sulcus (STS), our knowledge of the anatomy of this sulcus is still limited by a large individual variability. In particular, an accurate characterization of the "plis de passage" (PPs), annectant gyri inside the fold, is lacking to explain this variability. Performed on 90 subjects of the HCP database, our study revealed that PPs constitute landmarks that can be identified from the geometry of the STS walls. They were found associated with a specific U-shape white-matter connectivity between the two banks of the sulcus, the amount of connectivity being related to the depth of the PPs. These findings raise new hypotheses regarding the spatial organization of PPs, the relation between cortical anatomy and structural connectivity, as well as the possible role of PPs in the regional functional organization.

Anatomo-functional correspondence in the superior temporal sulcus.

The superior temporal sulcus (STS) is an intriguing region both for its complex anatomy and for the multiple functions that it hosts. Unfortunately, most studies explored either the functional organization or the anatomy of the STS only. Here, we link these two aspects by investigating anatomo-functional correspondences between the voice-sensitive cortex (Temporal Voice Areas) and the STS depth. To do so, anatomical and functional scans of 116 subjects were processed such as to generate individual surface maps on which both depth and functional voice activity can be analyzed. Individual depth profiles of manually drawn STS and functional profiles from a voice localizer (voice > non-voice) maps were extracted and compared to assess anatomo-functional correspondences. Three major results were obtained: first, the STS exhibits a highly significant rightward depth asymmetry in its middle part. Second, there is an anatomo-functional correspondence between the location of the voice-sensitive peak and the deepest point inside this asymmetrical region bilaterally. Finally, we showed that this correspondence was independent of the gender and, using a machine learning approach, that it existed at the individual level. These findings offer new perspectives for the understanding of anatomo-functional correspondences in this complex cortical region.

The protective effects of nutritional antioxidant therapy on Ehrlich solid tumor-bearing mice depend on the type of antioxidant therapy chosen: histology, genotoxicity and hematology evaluations.

Strong evidence indicates that reactive oxygen species (ROS) play an important role in the initiation as well as the promotion phase of carcinogenesis. Studies support the role of ROS in cancer, in part, by showing that dietary antioxidants act as cancer-preventive agents. Although results are promising, the research on this topic is still controversial. Thus, the aim of this study was to investigate whether vitamins C, E and pequi oil can, individually, provide prevention and/or be used afterward as an adjuvant in cancer therapy. Ehrlich solid tumor-bearing mice received antioxidant as follows: before tumor inoculation, before and after tumor inoculation (continuous administration), and after tumor inoculation; morphometric analyses of tumor, genotoxicity and hematology were then carried out. Antioxidant administrations before tumor inoculation effectively inhibited its growth in the three experimental protocols, but administrations after the tumor's appearance accelerated tumor growth and favored metastases. Continuous administration of pequi oil inhibited the tumor's growth, while the same protocol with vitamins E and C accelerated it, favoring metastasis and increasing oxidative stress on erythrocytes. Except for continuous administration with vitamin E, the development of ascites tumor metastases was linked with increased inflammation. Results suggest that the efficiency and applicability of antioxidants in the medical clinic can depend not only on the nature of the antioxidant, the type and stage of cancer being treated and the prevailing oxygen partial pressure in the tissues, but also on the type of antioxidant therapy chosen.

Impaired recognition of fear in voices and reduced anxiety after unilateral temporal lobe resection.

It has been reported that bilateral amygdala damage in humans compromises the recognition of fear and anger in nonverbal vocalizations (Scott et al., 1997). We addressed the possibility that unilateral temporal lobe damage might be sufficient to impair fear recognition in voices. For this purpose, we tested patients after left (n=10) or right (n=8) medial temporal lobe resection for the relief of intractable epilepsy using a set of nonverbal vocalizations (Belin, Fillion-Bilodeau, & Gosselin, 2008). To focus more narrowly on the role of amygdala subparts, we differentiated patients with complete amygdala damage vs. damage limited to the basolateral complex of the amygdala. The results confirmed for the first time that unilateral amygdala lesion including the basolateral complex can selectively impair recognition of fear and surprise expressed by voices, supporting the notion that the amygdala is a multimodal structure. Interestingly, this impairment was observed in patients with incomplete resection of the amygdala that spared the central nucleus and the corticomedial complex, suggesting that a resection of the basolateral complex is sufficient to affect fear recognition. Given that fear has often been considered as a precursor of anxiety, we also investigated the effect of such lesions on self-reported anxiety. The same patients appeared to be less anxious than control participants in their mood questionnaires. The association of impaired fear perception and decreased anxiety level is considered in the light of recent human and animal data, providing support for a neurobiological basis of mood changes in patients with unilateral temporal lobe damage.

Voice discrimination in cochlear-implanted deaf subjects.

The human voice is important for social communication because voices carry speech and other information such as a person's physical characteristics and affective state. Further restricted temporal cortical regions are specifically involved in voice processing. In cochlear-implanted deaf patients, the processor alters the spectral cues which are crucial for the perception of the paralinguistic information of human voices. The aim of this study was to assess the abilities of voice discrimination in cochlear-implant (CI) users and in normal-hearing subjects (NHS) using a CI simulation (vocoder). In NHS the performance in voice discrimination decreased when reducing the spectral information by decreasing the number of channels of the vocoder. In CI patients with different delays after implantation we observed a strong impairment in voice discrimination at time of activation of the neuroprosthesis. No significant improvement can be detected in patients after two years of experience of the implant while they have reached a higher level of recovery of speech perception, suggesting a dissociation in the dynamic of functional recuperation of speech and voice processing. In addition to the lack of spectral cues due to the implant processor, we hypothesized that the origin of such deficit could derive from a crossmodal reorganization of the temporal voice areas in CI patients.

Hearing loss severity: impaired processing of formant transition duration.

Normal hearing listeners exploit the formant transition (FT) detection to identify place of articulation for stop consonants. Neuro-imaging studies revealed that short FT induced less cortical activation than long FT. To determine the ability of hearing impaired listeners to distinguish short and long formant transitions (FT) from vowels of the same duration, 84 mild to severe hearing impaired listeners and 5 normal hearing listeners were asked to detect 10 synthesized stimuli with long (200 ms) or short (40 ms) FT among 30 stimuli of the same duration without FT. Hearing impaired listeners were tested with and without hearing aids. The effect of the difficulty of the task (short/long FT) was analysed as a function of the hearing loss with and without hearing aids. Normal hearing listeners were able to detect every FT (short and long). For hearing impaired listeners, the detection of long FT was better than that of short ones irrespective of their degree of hearing loss. The use of hearing aids improved detection of both kinds of FT; however, the detection of long FT remained much better than the detection of the short ones. The length of FT modified the ability of hearing impaired patients to detect FT. Short FT had access to less cortical processing than long FT and cochlea damages enhanced this specific deficit in short FT brain processing. These findings help to understand the limit of deafness rehabilitation in the time domain and should be taken into account in future devices development.

Toxicity-based selection of Escherichia coli mutants for functional recombinant protein production: application to an antibody fragment.

We propose a novel approach to the selection of Escherichia coli bacterial strains improved for the production of recombinant functional proteins. This approach is based on aggregation-induced toxicity of recombinant proteins. We show that selection of clones displaying a reduced toxicity is an efficient means of isolating bacteria producing recombinant protein with reduced aggregation in favour of correct folding. For an efficient selection, we found that time of toxicity induction must be precisely determined and recombinant protein must be expressed as a fusion with a protein whose activity is easily detectable on plates, thus allowing elimination of non-productive mutants. Choosing the expression to the periplasmic space of an scFv fragment fused to the N-terminus of alkaline phosphatase as a model, we selected chromosomal mutations that reduce aggregation-induced toxicity and showed that they concomitantly improve production of a functional recombinant hybrid. The effects of the mutations isolated could then be cumulated with those of other strategies used for recombinant scFv production. Thus, we could ensure a 6- to 16-fold increase in production of a functional scFv-PhoA hybrid. This is the first report demonstrating the possibility of directly selecting on agar plates E.coli strains improved for functional recombinant protein production from a large bacterial mutant library.

[Auditory perception and language: functional imaging of speech sensitive auditory cortex]. / Perception auditive et langage: imagerie fonctionnelle du cortex auditif sensible au langage.

Since the description of cortical deafness, it has been known that the superior temporal cortex is bilaterally involved in the initial stages of language auditory perception but the precise anatomical limits and the function of this area remain debated. Here we reviewed more than 40 recent papers of positron emission tomography and functional magnetic resonance imaging related to language auditory perception, and we performed a meta-analysis of the localization of the peaks of activation in the Talairach's space. We found 8 studies reporting word versus non-word listening contrasts with 54 activation peaks in the temporal lobes. These peaks clustered in a bilateral and well-limited area of the temporal superior cortex, which is here operationally defined as the speech sensitive auditory cortex. This area is more than 4cm long, located in the superior temporal gyrus and the superior temporal sulcus, both anterior and posterior to Heschl's gyrus. It do not include the primary auditory cortex nor the ascending part of the planum temporale. The speech sensitive auditory cortex is not activated by pure tones, environmental sounds, or attention directed toward elementary components of a sound such as intensity, pitch, or duration, and thus has some specificity for speech signals. The specificity is not perfect, since we found a number of non-speech auditory stimuli activating the speech sensitive auditory cortex. Yet the latter studies always involve auditory perception mechanisms which are also relevant to speech perception either at the level of primitive auditory scene analysis processes, or at the level of specific schema-based recognition processes. The dorsal part of the speech sensitive auditory cortex may be involved in primitive scene analysis processes, whereas distributed activation of this area may contribute to the emergence of a broad class of "voice" schemas and of more specific "speech schemas/phonetic modules" related to different languages. In addition, this area is activated by language-related lip movement, suggesting that a multimodal integration of the auditory and the visual information relevant in speech perception occurs at this level. Finally, there is a task-related top-down modulation of the pattern of activation of the speech sensitive auditory cortex which may reflect the fact that the different parts of this structure are connected to different down-stream cortical regions involved in the neural processing of different types of tasks.

Spectral and temporal processing in human auditory cortex.

We used positron emission tomography to examine the response of human auditory cortex to spectral and temporal variation. Volunteers listened to sequences derived from a standard stimulus, consisting of two pure tones separated by one octave alternating with a random duty cycle. In one series of five scans, spectral information (tone spacing) remained constant while speed of alternation was doubled at each level. In another five scans, speed was kept constant while the number of tones sampled within the octave was doubled at each level, resulting in increasingly fine frequency differences. Results indicated that (i) the core auditory cortex in both hemispheres responded to temporal variation, while the anterior superior temporal areas bilaterally responded to the spectral variation; and (ii) responses to the temporal features were weighted towards the left, while responses to the spectral features were weighted towards the right. These findings confirm the specialization of the left-hemisphere auditory cortex for rapid temporal processing, and indicate that core areas are especially involved in these processes. The results also indicate a complementary hemispheric specialization in right-hemisphere belt cortical areas for spectral processing. The data provide a unifying framework to explain hemispheric asymmetries in processing speech and tonal patterns. We propose that differences exist in the temporal and spectral resolution of corresponding fields in the two hemispheres, and that they may be related to anatomical hemispheric asymmetries in myelination and spacing of cortical columns.

Oversynthesis of a new Escherichia coli small RNA suppresses export toxicity of DsbA'-PhoA unfoldable periplasmic proteins.

In Escherichia coli, the DsbA'-PhoA hybrid proteins carrying an unfoldable DsbA' fragment can be targeted to the envelope, where they exert their toxicity. Hybrid proteins stick to the periplasmic face of the inner membrane and paralyze the export mechanism, becoming lethal if sufficiently overproduced and if not degraded by the DegP protease (A. Guigueno, P. Belin, and P. L. Boquet, J. Bacteriol. 179:3260-3269, 1997). We isolated a multicopy suppressor that restores viability to a degP strain without modifying the expression level of the toxic fusion. Suppression does not involve activation of the known envelope stress-combative pathways, the Cpx pathway and the sigma(E) regulon. Subclone analysis of the suppressor revealed a 195-bp DNA fragment that is responsible for toxicity suppression. The cloned gene, called uptR, is approximately 130 bp long (including the promoter and a transcription termination signal) and is transcribed into a small RNA (92 nucleotides). Using site-directed mutagenesis, we found that UptR RNA does not require translation for toxicity suppression. UptR-mediated action reduces the amount of membrane-bound toxic hybrid protein. UptR RNA is the first example of a small RNA implicated in extracytoplasmic toxicity suppression. It appears to offer a new way of suppressing toxicity, and its possible modes of action are discussed.

Temporal lobe dysfunction in childhood autism: a PET study. Positron emission tomography.

OBJECTIVE: The nature of the underlying brain dysfunction of childhood autism, a life-long severe developmental disorder, is not well understood. Although researchers using functional brain imaging have attempted to contribute to this debate, previous studies have failed to report consistent localized neocortical brain dysfunction. The authors reasoned that early methods may have been insensitive to such dysfunction, which may now be detectable with improved technology. METHOD: To test this hypothesis, regional cerebral blood flow was measured with positron emission tomography (PET) in 21 children with primary autism and in 10 nonautistic children with idiopathic mental retardation. Autistic and comparison groups were similar in average age and developmental quotients. The authors first searched for focal brain dysfunction in the autistic group by using a voxel-based whole brain analysis and then assessed the sensitivity of the method to detect the abnormality in individual children. An extension study was then performed in an additional group of 12 autistic children. RESULTS: The first autistic group had a highly significant hypoperfusion in both temporal lobes centered in associative auditory and adjacent multimodal cortex, which was detected in 76% of autistic children. Virtually identical results were found in the second autistic group in the extension study. CONCLUSIONS: PET and voxel-based image analysis revealed a localized dysfunction of the temporal lobes in school-aged children with idiopathic autism. Further studies will clarify the relationships between these temporal abnormalities and the perceptive, cognitive, and emotional developmental abnormalities characteristic of this disorder.

A cortical region sensitive to auditory spectral motion.

The functional architecture of human auditory cortex is still poorly understood compared with that of visual cortex, yet anatomical and electrophysiological studies in non-human primates suggest that the auditory cortex also might be functionally specialized, in a model of parallel and hierarchical organization. In particular, spectral changes such as the formant transitions of speech, or spectral motion (SM) by analogy with visual motion, could be processed in specialized cortical regions. In this study, positron emission tomography (PET) was used to identify which auditory cortical region are involved in SM analysis. We found that a bilateral secondary auditory cortical region, located in the caudal-lateral belt of auditory cortex, was more sensitive to auditory stimuli containing spectral changes than to matched stimuli with a stationary spectral profile. This result suggests that analogies between sensory systems could prove useful in the research into the functional organization of the auditory cortex.

Using cultural beliefs and patterns to improve mammography utilization among African-American women: the Witness Project.

Breast cancer and early detection of the disease is a significant issue for all women. Moreover, the sociocultural implications in the differential mortality rates increased interest in possible barriers to screening practices. Recently, a number of studies have investigated African Americans' cultural beliefs associated with breast cancer. This study is based upon qualitative focus group data gathered from 1989 to 1991 and 1996. This article provides focus group data that informed a culturally competent community-based cancer education program for African-American women--the Witness Project. Analysis of the qualitative data along with the quantitative outcome data revealed a direct relationship between cultural beliefs and patterns with mammography utilization. The once perceived cultural barriers can actually be applied as a cultural intervention strategy to improve breast cancer screening initiatives designed specifically for African-American women.

Voice-selective areas in human auditory cortex.

The human voice contains in its acoustic structure a wealth of information on the speaker's identity and emotional state which we perceive with remarkable ease and accuracy. Although the perception of speaker-related features of voice plays a major role in human communication, little is known about its neural basis. Here we show, using functional magnetic resonance imaging in human volunteers, that voice-selective regions can be found bilaterally along the upper bank of the superior temporal sulcus (STS). These regions showed greater neuronal activity when subjects listened passively to vocal sounds, whether speech or non-speech, than to non-vocal environmental sounds. Central STS regions also displayed a high degree of selectivity by responding significantly more to vocal sounds than to matched control stimuli, including scrambled voices and amplitude-modulated noise. Moreover, their response to stimuli degraded by frequency filtering paralleled the subjects' behavioural performance in voice-perception tasks that used these stimuli. The voice-selective areas in the STS may represent the counterpart of the face-selective areas in human visual cortex; their existence sheds new light on the functional architecture of the human auditory cortex.

[Mechanisms of aphasia recovery and brain imaging]. / Mécanismes de la récupération de l'aphasie et imagerie cérébrale.

Aphasia recovery may depend on right hemisphere or non-lesioned left hemisphere structures, pre-morbid brain language organization, and de novo learning of language. Here we review the brain imaging evidence supporting these different hypotheses. CT-scan studies have investigated the prognosis value of size and site of left hemisphere lesions. The size of the lesion is a global but not an individual predictor of the initial severity and subsequent recovery of aphasia. Studies on the site of the lesion have given different results for verbal expression and comprehension. There is no consensus on a single critical site for recovery of verbal expression in non-fluent aphasia, which may depend on sub-cortical more than cortical extend of the lesion. Conversely the extend of the lesion in the superior temporal gyrus emerges as a critical negative factor for comprehension recovery. Rest measurements of brain metabolism have consistently shown that aphasia severity depends much more on the degree of dysfunction of language-related areas in the left hemisphere than on the site of the lesion it-self. This suggests that aphasia recovery may depend on metabolic dysfunction recovery in peri-lesional structures. More recently, activation studies have shown consistent right hemisphere activation during language tasks in aphasic subjects, but their role in recovery remains debated. It is likely limited, and may depend on atypical pre-morbid language lateralization. Left hemisphere activations are also found in aphasic patients. They are often relocalized in peri-lesional areas, and emerge in most studies as the main factor of aphasia recovery.

Event-related fMRI of the auditory cortex.

An event-related protocol was designed to permit auditory fMRI studies minimally affected by the echo-planar noise artifact; a long time interval (TR = 10 s) between each cerebral volume acquisition was combined with stroboscopic data acquisition, and event-related curves were reconstructed with a 1-s resolution. The cerebral hemodynamic-response time course to a target auditory stimulus was measured in five individual subjects using this method. Clear bell-shaped event-related responses were observed bilaterally in all individuals in primary auditory cortex (A1) as well as in laterally extending secondary cortical fields. Group-average event-related curves attained their maxima (0.5-0.7%) 3 s after stimulus onset in A1 (4 s for more anterior and lateral regions of auditory cortex), and signal had returned to near-baseline level 6 s after stimulus onset. The stroboscopic event-related method appeared effective in minimizing effects of the interaction between scanning noise and experimental auditory stimulation; it adds useful temporal information to the spatial resolution afforded by fMRI in studies of human auditory function, while allowing presentation of auditory stimuli on a silent background.

On the role of the cis-proline residue in the active site of DsbA.

In addition to the Cys-Xaa-Xaa-Cys motif at position 30-33, DsbA, the essential catalyst for disulfide bond formation in the bacterial periplasm shares with other oxidoreductases of the thioredoxin family a cis-proline in proximity of the active site residues. In the variant DsbA(P151A), this residue has been changed to an alanine, an almost isosteric residue which is not disposed to adopt the cis conformation. The substitution strongly destabilized the structure of DsbA, as determined by the decrease in the free energy of folding. The pKa of the thiol of Cys30 was only marginally decreased. Although in vivo the variant appeared to be correctly oxidized, it exhibited an activity less than half that of the wild-type enzyme with respect to the folding of alkaline phosphatase, used as a reporter of the disulfide bond formation in the periplasm. DsbA(P151A) crystallized in a different crystal form from the wild-type protein, in space group P2(1) with six molecules in the asymmetric unit. Its X-ray structure was determined to 2.8 A resolution. The most significant conformational changes occurred at the active site. The loop 149-152 adopted a new backbone conformation with Ala151 in a trans conformation. This rearrangement resulted in the loss of van der Waals interactions between this loop and the disulfide bond. His32 from the Cys-Xaa-Xaa-Cys sequence presented in four out of six molecules in the asymmetric unit a gauche conformation not observed in the wild-type protein. The X-ray structure and folding studies on DsbA(P151A) were consistent with the cis-proline playing a major role in the stabilization of the protein. A role for the positioning of the substrate is discussed. These important properties for the enzyme function might explain the conservation of this residue in DsbA and related proteins possessing the thioredoxin fold.

Three-dimensional reconstruction of the human central sulcus reveals a morphological correlate of the hand area.

One way to improve our understanding of cortical anatomy is to visualize the three-dimensional (3D) shape of the cerebral sulci which is normally hidden. Here, we reconstructed the 3D morphology of the central sulcus (CS) in 17 normal subjects, using conventional magnetic resonance images and dedicated software. We found that the 3D morphology was remarkably consistent in all central sulci. Our analyses revealed three different regions (upper, middle and lower), which were easily identifiable by morphological criteria and sharply interconnected in the reconstructed CS. These morphological regions appear to have a strong functional significance, since the middle region corresponded precisely to the 'hand area', as verified by hand vibration positron emission tomography activation studies in eight cases. These data suggest that the 3D anatomy of the cerebral cortex may facilitate sulcal recognition, and sulcal subdivision into smaller morphological elements, bearing remarkable relationships with functional cortical maps.

Lateralization of speech and auditory temporal processing.

To investigate the role of temporal processing in language lateralization, we monitored asymmetry of cerebral activation in human volunteers using positron emission tomography (PET). Subjects were scanned during passive auditory stimulation with nonverbal sounds containing rapid (40 msec) or extended (200 msec) frequency transitions. Bilateral symmetric activation was observed in the auditory cortex for slow frequency transitions. In contrast, left-biased asymmetry was observed in response to rapid frequency transitions due to reduced response of the right auditory cortex. These results provide direct evidence that auditory processing of rapid acoustic transitions is lateralized in the human brain. Such functional asymmetry in temporal processing is likely to contribute to language lateralization from the lowest levels of cortical processing.