PubMed Health⌕ Search

Biomedical subjects

Martine Meunier

Publications and source records attributed to Martine Meunier.

15 recordsLinked to original sources

Pathological response to preoperative concurrent chemo-radiotherapy for breast cancer: results of a phase II study.

This study evaluated, in terms of pathological complete response (pCR) and acute toxicity, preoperative concurrent (5-fluorouracil (5-FU)-vinorelbine) chemoradiotherapy for large breast cancers. A total of 60 women were included in the study. Chemotherapy consisted of 4 cycles of 5-FU, 500 mg/m2/d, continuous infusion (d1-d5) and vinorelbine, 25 mg/m2 (d1; d6). Starting with the second cycle, radiotherapy delivered 50 Gy to the breast and 46 Gy to the internal mammary and supra/infra-clavicular lymph nodes. Breast surgery and axillary lymph node dissection were then performed. Four patients did not complete their chemotherapy. Breast conservation was possible in 69% of patients. The rate of pCR was 27%. Three factors were associated with pCR: histological grade 3, absence of hormonal receptors and high mitotic index. Grade 4 haematological toxicity occurred in 22% of patients. In conclusion, chemoradiotherapy demonstrated good efficacy, both in terms of pCR and in allowing breast conservation with acceptable tolerance.

Adult↗

Responses to affective stimuli in monkeys with entorhinal or perirhinal cortex lesions.

Recent efforts to define the functions of the primate rhinal (entorhinal and perirhinal) cortical areas have focused on their interaction with the hippocampus in the mediation of normal memory. Less is known on the functional meaning of their strong connections to the amygdala, a key substrate for emotion. A previous study (Meunier and Bachevalier, 2002) showed evidence that complete rhinal ablations yield changes in monkeys' behavioral responses to affectively salient stimuli. Here, we studied monkeys with separate entorhinal or perirhinal ablations in the same paradigm, where responses were triggered by four stimuli: an unfamiliar human, a conspecific stimulus, a toy snake, and a familiar (generally rewarded) junk object. The two separate lesions produced similar changes, and each replicated the effects of complete rhinal lesions (i.e., attenuated affiliation and enhanced defense). Failure to modulate responses based on previous experience (i.e., memory difficulties) may explain these affective changes. This interpretation does not account, however, for the sparing of some memory-dependent modulations of defense, nor for the lack of correlation between the animals' affective changes and their own recognition memory performance. Alternatively, rhinal damage may introduce a negative bias in the risk assessment of affectively salient stimuli, a proposal more compatible with Gray and McNaughton's (2000) anxiety-centered view of medial temporal functions, than with prominent mnemonic/perceptual functional models of the hippocampal/rhinal duo. Reconciling the two perspectives may improve our understanding of rhinal functions.

Affect↗

Conditional visuo-motor learning and dimension reduction.

Conditional visuo-motor learning consists in learning by trial and error to associate visual cues with correct motor responses, that have no direct link. Converging evidence supports the role of a large brain network in this type of learning, including the prefrontal and the premotor cortex, the basal ganglia BG and the hippocampus. In this paper we focus on the role of a major structure of the BG, the striatum. We first present behavioral results and electrophysiological data recorded from this structure in monkeys engaged in learning new visuo-motor associations. Visual stimuli were presented on a video screen and the animals had to learn, by trial and error, to select the correct movement of a joystick, in order to receive a liquid reward. Behavioral results revealed that the monkeys used a sequential strategy, whereby they learned the associations one by one although they were presented randomly. Human subjects, tested on the same task, also used a sequential strategy. Neuronal recordings in monkeys revealed learning-related modulations of neural activity in the striatum. We then present a mathematical model inspired by viability theory developed to implement the use of strategies during learning. This model complements existing models of the BG based on reinforcement learning RL, which do not take into account the use of strategies to reduce the dimension of the learning space.

Basal Ganglia↗

Prehension movements in the macaque monkey: effects of perturbation of object size and location.

While the neural bases of prehension have been extensively studied in monkeys, a few kinematic studies have examined their prehension behavior. Recently (Roy et al. 2000, 2002), we have described the kinematics of reaching and grasping in freely behaving monkeys under normal conditions by applying the high-resolution recording techniques (Optotrak system) and behavioral paradigms used in humans. Here we determined whether online movement reorganization observed in monkeys following sudden changes of either object size or location at movement onset is similar to that observed in humans. We found that changing object size led to rapid on-flight re-calibration of the different movement parameters, eventually preserving the unitary aspect of the movement with a minor time cost. By contrast, a shift in object location triggered a massive time-consuming reorganization. Re-directed movements appeared as a concatenation of two sub-movements: a first one directed to the initial object and a second one directed to the new object location. These findings first complement our earlier studies in providing further evidence of the similarities between monkey and human prehension. Second, they suggest that the two components of prehension, reaching and grasping, interact through coordination mechanisms that are more efficient to correct for size than for location perturbation. This difference may reflect a hierarchical organization in which reaching would be the subordinate of grasping in both primate species.

Animals↗

Stereotactic radioguided surgery by siteSelect for subclinical mammographic lesions.

BACKGROUND: We defined the indications for and evaluated the results of a new technique for radioguided surgery, the SiteSelect system. The procedure allows en-bloc resection of the breast parenchyma under local anesthesia. METHODS: This prospective study was based on 167 patients operated on between December 2000 and October 2003 with 2 phases. The first step was an evaluation of the feasibility of the procedure with the 15-mm cannula, and the second was therapeutic with the 22-mm cannula. RESULTS: The mean duration of the procedure was 42 minutes. In 96.9% of procedures, the lesion was excised successfully. Only one complication (hematoma) and two failures and were observed. Histological examination revealed benign disease in 65.8% of cases and cancer in 34.2% of cases. In the latter cases, the specimen margins were histologically involved in 86.2% of cases with the 15-mm procedure and in 41% with the 22-mm procedure. During the first evaluation, all patients with a cancer underwent systematic surgical re-excision: residual tumor was present in 18 cases (64.2%). The biopsy was painless for 88 patients, and the cosmetic result was good in all cases. CONCLUSIONS: This study shows that the SiteSelect procedure allows resection of the lesion in 96.9% of cases. Combined with complementary surgical lumpectomy during the same operation, this procedure achieved a success rate of 98.7%. In the case of cancer, the 15-mm cannula is not wide enough to allow free margins. The use of a new 22-mm cannula, currently under evaluation, might solve this problem.

Adult↗

MR quantification of the washout changes in breast tumors under preoperative chemotherapy: feasibility and preliminary results.

OBJECTIVE: The objective of our study was to describe and determine the feasibility of an MR washout quantification method in patients with breast cancer under preoperative chemotherapy. MATERIALS AND METHODS: Nineteen patients with breast T2 or T3 tumors were enrolled in a previous study for tumor response evaluation during chemotherapy based on dynamic contrast-enhanced MRI. We retrospectively used the dynamic acquisition data to produce parametric images representing the washout pattern. Two radiologists unaware of the final pathologic results measured the volume of pixels exhibiting washout within the tumor before chemotherapy (volume 1), after two courses of chemotherapy (volume 2), and before surgery after four courses of chemotherapy (volume 3). The interobserver variability and intraobserver variability were calculated to evaluate the reproducibility of our method with the Pearson's correlation coefficient and the concordance correlation coefficient. We correlated the washout changes by means of a Student's t test and noted the histopathologic final outcome. RESULTS: A washout pattern was present in all patients on the initial MR study. The quantification method of the washout changes was reproducible with good interobserver agreement (r = 0.85, p < 10(-5)) and an excellent intraobserver agreement (r = 0.94, p < 10(-5)). A significant decrease of the washout volume was observed after two courses of chemotherapy (p = 0.004), whereas no significant modification was observed between two and four courses of chemotherapy (p = 0.52). CONCLUSION: Quantification of the washout variation in breast tumor based on the use of parametric images is feasible and reproducible. It may add information to the evaluation of tumor response to preoperative therapy.

Adult↗

Histological margin assessment for breast ductal carcinoma in situ: precision and implications.

Local recurrence after lumpectomy for ductal carcinoma in situ (DCIS) is a major concern and is related to residual disease in the breast. We studied the predictive value of lumpectomy margins for residual DCIS and compared our results and pathological processing techniques with those published in the literature. Margin status was determined for 89 patients with screen-detected DCIS who had lumpectomy and re-excision, for the presence and extent of residual disease. Margin width was defined as the narrowest distance between tumor and any inked margin or, where margins were positive, classified into focal involvement (<1 mm of the inked surface involved), minimal (>or=1<15 mm) and extensive (>or=15 mm). The amount of residual tumor was quantified according to the number of ducts involved with tumor: small (fewer than 10 ducts) or large (10 or more ducts) residuum. The initial margin status was a significant predictor for the presence of residual tumor in re-excision specimens (P=0.006). There was residual tumor in 44 and 45% of close non-involved (>1 and 25 mm,respectively, showing residual disease. The presence of residual tumor was not significantly related to age, mammographic appearance, nuclear grade or intraductal necrosis. The initial margin status was found to predict for the amount of residual tumor. With careful margin assessment, margin status after lumpectomy for DCIS can be used to predict for the presence and amount of residual tumor in the breast and is a guide to further management decisions. A standard for margin status reporting and pathological processing of screen-detected DCIS in situ lesions will help in the interpretation of data from different institutions.

Adult↗

MRI for surgical planning in patients with breast cancer who undergo preoperative chemotherapy.

OBJECTIVE: Accurate presurgical evaluation of residual disease appears essential for successful clinical outcome in patients with breast cancer who are undergoing chemotherapy. Our objective was to study the impact on surgical planning of adding serial MRI evaluations of the tumor to standard non-MRI assessments. MATERIALS AND METHODS: MR images of breast tumors obtained before, during, and after preoperative chemotherapy were reviewed in 30 patients. Tumor response was assessed using both size and morphologic MRI criteria. We compared the actual surgical decisions made prospectively on the basis of standard (clinical, mammographic, and sonographic) assessments of response with decisions that would have been made had MRI findings also been considered. MRI investigators were blinded to the ultimate surgical results. Successful breast-conserving surgery was judged on pathologic confirmation of excision margins that were negative for cancer. RESULTS: The standard evaluation led to 16 successful breast-conserving and 14 mastectomy procedures. Using MRI results would have led to major beneficial therapeutic changes in six (20%) of the 30 patients: five patients undergoing primary mastectomy (chemotherapy avoided) and one patient undergoing postchemotherapy mastectomy (unsuccessful breast-conserving surgery avoided). MRI would have added valuable information in 14 (46.7%) of the 30 patients. In seven (23.3%) of the 30 patients, the decision to perform postchemotherapy mastectomy would have been unchanged. In one patient (3.3%), MRI results would not have prevented unsuccessful breast-conserving surgery. In two patients (6.6%), MRI results would have prevented successful breast-conserving surgery from being performed. CONCLUSION: Although the ultimate incidence of breast conservation was potentially similar for the patients (16/30, 53%) in whom the standard evaluation was used and for the patients (14/30, 47%) in whom the MRI-added evaluation was used, MRI was useful in establishing the final treatment earlier in the process, avoiding unnecessary preoperative chemotherapy, or selecting high-risk breast-conserving procedures.

Adult↗

Reactions to familiar and novel objects in infant monkeys with neonatal temporal lesions.

Adult monkeys with late temporal lobe damage are known to touch and mouth objects compulsively, even unknown objects. To determine whether infants with early temporal damage display this symptom as well, 9-month-old rhesus monkeys with neonatal ablations of either the medial temporal lobe or inferior temporal cortex were exposed to four objects, two familiar and two novel. All operated infants were less active/more withdrawn than controls and showed neither exaggerated object manipulation nor hyperorality. Furthermore, like controls, they touched novel objects less than they touched familiar ones. Thus, infants with neonatal medial or inferior temporal ablations did not display the compulsive exploration evidenced after similar lesions in adulthood and retained some ability to detect novelty despite their known memory impairments.

Animals↗

Comparison of emotional responses in monkeys with rhinal cortex or amygdala lesions.

Four emotionally arousing stimuli were used to probe the behavior of monkeys with bilateral ablations of the entorhinal and perirhinal cortex. The monkeys' behavioral changes were then contrasted with those observed earlier (M. Meunier, J. Bachevalier, E. A. Murray, L. Málková, & M. Mishkin, 1999) in monkeys with either neurotoxic or aspiration lesions of the neighboring amygdala. Rhinal cortex ablations yielded several subtle behavioral changes but none of them resembled any of the disorders typically seen after amygdalectomies. The changes produced by rhinal damage took mainly the form of heightened defensiveness and attenuated submission and approach responses; that is, just the opposite of some of the most distinctive symptoms following amygdala damage. These findings raise the possibility that the rhinal cortex and amygdala have distinct, interactive functions in normal behavioral adaptation to affective stimuli.

Aggression↗

Prehension movements in the macaque monkey: effects of object size and location.

Prehension movements were examined in freely behaving monkeys and compared with the well-known characteristics of human movements. The degree of independence of the components of movements (i.e., reaching and grasping) was investigated in animals trained to reach for and grasp three-dimensional objects. To this aim, the kinematics of prehension movements was recorded using an Optotrak system in two tasks. In one task, monkeys grasped a small or a large object (size task), in the other, they grasped an object of constant size placed at three different spatial locations (location task). We found that object size and its location affected both reaching and grasping. In particular, in the size task, we found that the maximum grip aperture strongly depended on the selection of the grip and not only on the size of an object. Our results also revealed that, in monkeys as well as in humans, the reaching parameters are highly sensitive to task-related constraints such as accuracy demands. The results of the location task showed a difference between rightward and leftward movements, a pattern of grip aperture that varied across animals, and a large degree of coordination between the two components. These findings argue against a strict postulate of independence between the visuo-motor channels, favoring instead the idea of variable degrees of coordination between the reach and grasp components depending on the task demands. Finally, this work emphasizes the relevance of studying monkey's prehension movements as a useful step to the understanding of visuo-motor control in humans.

Animals↗

Spatial attention and memory versus motor preparation: premotor cortex involvement as revealed by fMRI.

Recent studies in both monkeys and humans indicate that the dorsal premotor cortex participates in spatial attention and working memory, in addition to its well known role in movement planning and execution. One important question is whether these functions overlap or are segregated within this frontal area. Single-cell recordings in monkeys suggest a relative specialization of the rostral portion of dorsal premotor cortex for attention and/or memory and of the caudal region for motor preparation. To test whether this possibility also holds true in humans, we used functional magnetic resonance imaging (fMRI) to compare, in the same set of subjects, brain activation related to strong spatial attention and memory demands to that elicited by long motor preparatory periods. The behavioral protocol was based on a task that had proved effective for dissociating neuronal properties related to these two functions in the monkey brain. The principle of the monkey task was that a first cue guided the focus of spatial attention and memory, whereas a second one instructed an arm movement. Based on this principle, two tasks were developed. One maximized spatial attention and memory demands by presenting long series of stimuli (4, 8, or 12) before the motor instructional cue, whereas the other extended the motor preparation phase by imposing long and variable delays (1-5.5 s) between the onset of the instructional cue and movement execution. The two tasks and their respective control conditions were arranged in two blocked-design sequences. The results indicate that the brain networks underlying the two functional domains overlap in the caudate nucleus and presupplementary motor area, and possibly in lateral prefrontal cortex as well, but involve different dorsal premotor fields. Motor preparation primarily recruited a dorsal premotor area located caudally, within the precentral gyrus (together with the supplementary motor area), whereas spatial attention and memory preferentially activated a more rostral site, in and anterior to the precentral sulcus (in addition to the posterior parietal cortex). These findings strengthen the idea that the primate dorsal premotor cortex contributes to both motor and nonmotor processes. Moreover, they corroborate emerging evidence from monkey physiology suggesting a relative functional segregation within this cortex, with attention to short-term storage of visuospatial information engaging a more rostral region than motor preparation.

Adult↗

Conditional visuo-motor learning in primates: a key role for the basal ganglia.

Sensory guidance of behavior often involves standard visuo-motor mapping of body movements onto objects and spatial locations. For example, looking at and reaching to grasp a glass of wine requires the mapping of the eyes and hand to the location of the glass in space, as well as the formation of a hand configuration appropriate to the shape of the glass. But our brain is far more than just a standard sensorimotor mapping machine. Through evolution, the brain of advanced mammals, in particular human and non-human primates, has acquired a formidable capacity to construct non-standard, arbitrary mapping using associations between external events and behavioral responses that bear no direct relationship. For example, we have all learned to stop at a red traffic light and to go at a green one, or to wait for a specific tone before dialing a phone number and to hang up when hearing a busy signal. These arbitrary associations are acquired through experience, thereby providing primates with a rich and flexible sensorimotor repertoire. Understanding how they are learned, and how they are recalled and used when the context requires them, has been one of the challenging issues for cognitive neuroscience. Valuable insights have been gained over the last two decades through the convergence of multiple complementary approaches. Human neuropsychology and experimental lesions in monkeys have identified a network of brain structures important for conditional sensorimotor associations, whereas imaging studies in healthy human subjects and electrophysiological recordings in awake monkeys have sought to identify the different functional processes underlying the overall function. The present review focuses on the contribution of a network linking the prefrontal cortex, basal ganglia, and dorsal premotor cortex, with special emphasis on results from recording experiments in monkeys. We will first review data pointing to a specific contribution of each component of the network to the performance of well-learned arbitrary visuo-motor associations, as well as data suggesting how novel associations are formed. Then we will propose a model positing that each component of the fronto-striatal network makes a specific contribution to the formation and/or execution of sensorimotor associations. In this model, the basal ganglia are thought to play a key role in linking the sensory, motor, and reward information necessary for arbitrary mapping.

Animals↗

[Long follow-up of breast cancer revealed by clustered microcalcifications without palpable mass].

OBJECTIVES: In the past two decades, nonpalpable breast cancer incidence has greatly increased by routine screening mammography. Microcalcifications are the most frequent radiological feature. METHODS: Between 1964 and 1994, 789 breast cancers revealed by clustered microcalcifications without palpable mass were treated at Institut Curie. Patients who had a past history of breast cancer or a contralateral cancer were eliminated like those with lobular carcinoma in situ. The definitive treatment was decided on the margins of the initial excision and the presence of microcalcifications on postoperative mammograms. RESULTS: Mean follow-up of the patients was 77 months (9-358). The treatment was conservative in 49.5% and radical in 50.5%. Histologically, 43.5% of the lesions were intraductal carcinoma, 25.5% were microinvasive and 31% were infiltrating cancers. Five and ten years overall survival were 98% and 92.5% respectively, 50% of the patients died from their breast cancer. This survival was identical for intraductal, microinvasive and invasive carcinomas without lymph node metastasis, but was less favorable in patients with node metastasis. There were no survival differences for the two treatment modalities, although local recurrences were more frequent in the conservative one. The 5-year recurrence rate was 3.5% for intraductal subtype, 4.4% for microinvasive and 6% for invasive cancers. The difference was not statistically significant. CONCLUSION: Under the impact of mammographic screening, sizable proportions of breast cancer patients are being seen in a totally nonpalpable state with either a very small invasive, microinvasive or intraductal breast cancer. These lesions have an excellent prognosis, and can benefit from less aggressive treatments. In the case of diffuse microcalcifications, where a radical treatment is indicated, skin sparing mastectomy can be easily done followed by immediate reconstructive surgery.

Adult↗