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P McGuire

Publications and source records attributed to P McGuire.

At least 19 recordsLinked to original sources
PubMed2006

Timing of covert articulation: an fMRI study.

Timing is an important constituent of speech and language. Different brain regions have been associated with time management functions such as time estimation and motor timing. This study aims to identify the less well known neural networks associated with timing of internally paced covert articulation. Functional MRI was performed on subjects who either spontaneously, or in response to a visual cue, covertly generated words every 2 s. Results show the involvement of anterior cingulate gyrus, right dorsolateral and inferior frontal and right inferior parietal cortices in a putatively modality independent circuit associated with timing of covert speech. Modality specific activation in the right temporal cortex may have reflected the involvement of this region in auditory-verbal processing.

Adult↗
PubMed2006

Pleiotropic role of VEGF-A in regulating fetal pulmonary mesenchymal cell turnover.

Tight regulation of VEGF-A production and signaling is important for the maintenance of lung development and homeostasis. VEGF null mice have provided little insight into the role of VEGF during the later stages of lung morphogenesis. Therefore, we examined the in vitro effects of autocrine and paracrine VEGF-A production and the inhibition of VEGF-A signaling on a Flk-1-negative subset of fetal pulmonary mesenchymal cells (pMC). We hypothesized that VEGF-A receptor signaling regulates turnover of fetal lung mesenchyme in a cell cycle-dependent manner. VEGF receptor blockade with SU-5416 caused cell spreading and decreased proliferation and bcl-2 localization. Nuclear expression of the cell cycle inhibitory protein, p21, was increased with SU-5416 treatment, and p27 was absent. Autocrine VEGF production by pMC resulted in proliferation and p21/p27-dependent contact inhibition. In contrast, exogenous VEGF-A increased cell progression through the cell cycle. Selective activation of Flt by placental growth factor demonstrated the importance of this receptor/kinase in the VEGF-A responsiveness of pMC. The expression and localization of the survival factor bcl-2 was dependent on VEGF. These results provide evidence that VEGF-A plays a critical role in the regulation of fetal pulmonary mesenchymal proliferation, survival, and the subsequent development of normal lung architecture through bcl-2 and p21/p27-dependent cell cycle control.

Animals↗
PubMed2005

Psychiatry in Europe.

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Cross-Cultural Comparison↗
PubMed2003

[Neural correlates of "negative" formal thought disorder].

Formal thought disorder (FTD) is a core feature of schizophrenia, but its pathophysiology is poorly understood. It can be conceptualised as 'positive' (e.g. incoherence, neologisms) or 'negative' (e.g. poverty of thought) thought disorder. We investigated the neural correlates of negative FTD. Blood oxygenation level-dependent (BOLD) contrast was measured using functional magnetic resonance imaging (fMRI) while six patients with schizophrenia and six healthy control subjects spoke about seven Rorschach inkblots for 3 min each. Varying degrees of thought-disordered speech were elicited during each run. In a within-subject design, the degree of negative thought disorder, conceptualised as 'poverty of speech' (Liddle et al. (2002) Thought and Language Index. Br J Psychiatry) was correlated with BOLD contrast in the two runs per patient showing the highest variance in this phenomenon. The degree of poverty of speech correlated positively mainly with activation in the right inferior parietal lobe (BA 40), middle frontal gyrus (BA 46), cuneus (BA 18), and the left posterior cingulate (BA 31). Negative correlations were evident in the left hippocampal/fusiform gyrus (BA 35/36/37). The severity of negative FTD correlates with activation in areas previously implicated in autobiographic episodic memory. During symptoms behaviourally characterised as negative, patients may experience rich memories and associations.

Adult↗
PubMed2003

Neural architectures for robot intelligence.

We argue that direct experimental approaches to elucidate the architecture of higher brains may benefit from insights gained from exploring the possibilities and limits of artificial control architectures for robot systems. We present some of our recent work that has been motivated by that view and that is centered around the study of various aspects of hand actions since these are intimately linked with many higher cognitive abilities. As examples, we report on the development of a modular system for the recognition of continuous hand postures based on neural nets, the use of vision and tactile sensing for guiding prehensile movements of a multifingered hand, and the recognition and use of hand gestures for robot teaching. Regarding the issue of learning, we propose to view real-world learning from the perspective of data-mining and to focus more strongly on the imitation of observed actions instead of purely reinforcement-based exploration. As a concrete example of such an effort we report on the status of an ongoing project in our laboratory in which a robot equipped with an attention system with a neurally inspired architecture is taught actions by using hand gestures in conjunction with speech commands. We point out some of the lessons learnt from this system, and discuss how systems of this kind can contribute to the study of issues at the junction between natural and artificial cognitive systems.

Action Potentials↗
PubMed2001

Cortical substrates for the perception of face actions: an fMRI study of the specificity of activation for seen speech and for meaningless lower-face acts (gurning).

Can the cortical substrates for the perception of face actions be distinguished when the superficial visual qualities of these actions are very similar? Two fMRI experiments are reported. Compared with watching the face at rest, observing silent speech was associated with bilateral activation in a number of temporal cortical regions, including the superior temporal sulcus (STS). Watching face movements of similar extent and duration, but which could not be construed as speech (gurning; Experiment 1b) was not associated with activation of superior temporal cortex to the same extent, especially in the left hemisphere. Instead, the peak focus of the largest cluster of activation was in the posterior part of the inferior temporal gyrus (right, BA 37). Observing silent speech, but not gurning faces, was also associated with bilateral activation of inferior frontal cortex (BA 44 and 45). In a second study, speechreading and observing gurning faces were compared within a single experiment, using stimuli which comprised the speaker's face and torso (and hence a much smaller image of the speaker's face and facial actions). There was again differential engagement of superior temporal cortex which followed the pattern of Experiment 1. These findings suggest that superior temporal gyrus and neighbouring regions are activated bilaterally when subjects view face actions--at different scales--that can be interpreted as speech. This circuitry is not accessed to the same extent by visually similar, but linguistically meaningless actions. However, some temporal regions, such as the posterior part of the right superior temporal sulcus, appear to be common processing sites for processing both seen speech and gurns.

Adult↗
PubMed2001

The balance between proteinases and inhibitors in a murine model of proliferative retinopathy.

PURPOSE: To examine the expression of matrix metalloproteinases (MMPs) and their inhibitors during the development of retinal neovascularization (NV) in a mouse model. METHODS: A well-characterized murine model of retinal NV was used to study the expression of specific MMPs (MMP-2, MMP-9, and MT1-MMP) and tissue inhibitor of metalloproteinases (TIMPs types 1, 2, and 3). NV of the retina was induced in mice by exposure to 75% O(2) from postnatal day (P)7 to P12, followed by return to room air from P12 to P17. Expression of MMP mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). In addition, retinal tissue removed from control (without NV) and experimental animals (with NV) was analyzed for the expression of TIMP-1, TIMP-2, and TIMP-3 mRNA and protein using RT-PCR and Western blot analysis. RESULTS: During the angiogenic period from P13 to P17, MMP-2 and -9, and MT1-MMP message expression increased in experimental retinas compared with control samples. The TIMP-2 message and protein levels increased steadily in the retina of control animals until P17. This was in contrast to that seen in the retinas of the experimental animals in which TIMP-2 message and protein remained low and significantly less than in control samples. There were no significant changes in TIMP-3 message levels in retinal tissues, and TIMP-1 message and protein were undetectable. CONCLUSIONS: Correlation was made at the mRNA and protein levels of TIMP expression compared with that of MMPs in a murine model of retinal NV, which suggests a temporal role for MMP-2 and -9, MT1-MMP, and TIMP-2 in new vessel formation in response to hypoxic stimulation.

Animals↗
PubMed2000

Silent speechreading in the absence of scanner noise: an event-related fMRI study.

In a previous study we used functional magnetic resonance imaging (fMRI) to demonstrate activation in auditory cortex during silent speechreading. Since image acquisition during fMRI generates acoustic noise, this pattern of activation could have reflected an interaction between background scanner noise and the visual lip-read stimuli. In this study we employed an event-related fMRI design which allowed us to measure activation during speechreading in the absence of acoustic scanner noise. In the experimental condition, hearing subjects were required to speechread random numbers from a silent speaker. In the control condition subjects watched a static image of the same speaker with mouth closed and were required to subvocally count an intermittent visual cue. A single volume of images was collected to coincide with the estimated peak of the blood oxygen level dependent (BOLD) response to these stimuli across multiple baseline and experimental trials. Silent speechreading led to greater activation in lateral temporal cortex relative to the control condition. This indicates that activation of auditory areas during silent speechreading is not a function of acoustic scanner noise and confirms that silent speechreading engages similar regions of auditory cortex as listening to speech.

Adult↗
PubMed2000

Long term psychiatric and cognitive effects of MDMA use.

Clinical case reports suggest that regular MDMA use can be associated with chronic psychiatric symptoms which persist after the cessation of drug use. Neuropsychological comparisons of regular MDMA users and controls also suggest that MDMA use may lead to memory deficits, with other cognitive processes relatively unaffected. This paper reviews these studies and discusses a number of methodological issues that impact on the interpretation of the findings. Methods for examining the biological effects of MDMA use in man are also outlined. Future research should clarify whether MDMA use has long term psychological effects, and if these are related to changes in central serotonergic function.

Chronic Disease↗
PubMed2000

Functional anatomy of auditory verbal imagery in schizophrenic patients with auditory hallucinations.

OBJECTIVE: This study investigated the functional neuroanatomy of inner speech and auditory verbal imagery in schizophrenic patients predisposed to auditory hallucinations. METHOD: Eight patients with schizophrenia with a history of prominent auditory hallucinations and six comparison subjects underwent functional magnetic resonance imaging while generating inner speech or imagining external speech. RESULTS: Patients showed no differences while generating inner speech but experienced a relatively attenuated response in the posterior cerebellar cortex, hippocampi, and lenticular nuclei bilaterally and the right thalamus, middle and superior temporal cortex, and left nucleus accumbens during auditory verbal imagery. CONCLUSIONS: Patients with schizophrenia who were prone to auditory hallucinations show attenuated activation when processing inner speech in areas implicated in verbal self-monitoring.

Adult↗
PubMed2000

Subjective imagery in obsessive-compulsive disorder before and after exposure therapy. Pilot randomised controlled trial.

BACKGROUND: Distressing mental imagery is hard to study experimentally in obsessive--compulsive disorder (OCD). AIMS: To develop a way to assess mental imagery in OCD during functional magnetic resonance imaging (fMRI). METHOD: A small randomised study, controlled for type and order of mental imagery and for treatment condition (exposure therapy guided by a computer or by a therapist, or relaxation guided by audio-tape). Before and after treatment, during fMRI scanning, patients imagined previously-rehearsed scenarios that evoked an urge to ritualise or non-OCD anxiety or a neutral state, and rated their discomfort during imagery. RESULTS: The method evoked greater discomfort during OCD imagery and anxiety (non-OCD) imagery than during neutral imagery. Discomfort was reduced by cancelling imagery. Discomfort during OCD imagery (but not during anxiety non-OCD imagery) fell after exposure therapy but not after relaxation. CONCLUSIONS: Results showed differences between OCD and non-OCD images and their change after successful treatment, and confirmed clinical suggestions that cancelling images reduced OCD discomfort. The method's success paves the way for further studies of mental imagery in OCD: for instance, during fMRI.

Adult↗
PubMed1999

Functional MR imaging of confounded hypofrontality.

Comparatively reduced blood flow to frontal brain regions in patients with schizophrenia (hypofrontality) has been frequently observed in the last 25 years. However, there is an inconstant quality to hypofrontality, suggesting either confounded observation of a static (trait-like) abnormality, or that it is a genuinely dynamic (state-like) phenomenon. Possible confounds in functional magnetic resonance imaging (fMRI) studies of hypofrontality are classified. Methods for assessment and correction of stimulus correlated motion (an extracerebral confound) are reviewed in the context of fMRI data acquired from five schizophrenic patients and five comparison subjects during performance of a verbal fluency task. Factorial analysis of these and other data, acquired from the same subjects during a semantic decision task, is used to exclude a number of possible intracerebral confounds. By analogy to the historical controversy concerning the appearance of the planet Saturn viewed through early telescopes, understanding the inconstancy of hypofrontality in schizophrenia is likely to progress more by theoretically driven experiments that exploit the repeatability of fMRI than by further technological development alone.

Analysis of Variance↗
PubMed1998

Effects of Great Lakes fish consumption on the immune system of Sprague-Dawley rats investigated during a two-generation reproductive study.

The effects of Great Lakes fish on food consumption, body and organ weights, and hematological parameters were investigated in the first- (F1) and second- (F2) generation Sprague-Dawley rats assigned to immunological studies. The parent- (F0) generation rats were fed either a control diet or diets containing 5 or 20% lyophilized chinook salmon from Credit River (Lake Ontario, LO) or Owen Sound (Lake Huron, LH). The F1 and F2 pups were exposed to the fish diet in utero, through the dam's milk to 21 days of age and through the respective diets to 13 weeks of age. The study included an F1-reversibility (F1-R) phase in which rats at 13 weeks of exposure to fish or control diets were switched to the control diet for 3 months. Statistically significant effects included increased growth rates in the F1 male rats fed the LH fish diets compared to those fed the LO fish diets; increased liver weights in the F2-generation male rats fed the LH-20% and LO-20% diets compared to those fed the 5% fish diets; reduced thymus weights in the F1-R female rats fed the LO-20% fish diet compared to those fed the LO-5% or LH-20% fish diets and in the F2 male rats fed the LO diets compared to those fed the LH diets; increased kidney weights in the F2 male rats fed the LH-20% diet compared to those fed the LH-5% or LO-20% diets; reduced but reversible effects on red blood cell (RBC), white blood cell (WBC), neutrophil, lymphocyte, and monocyte numbers in the F1-generation female rats fed the fish diets; reduced red blood cell (RBC), white blood cell (WBC), and lymphocyte numbers in the F2 male rats fed the LO diets compared to those fed the LH diets; and reduced WBC and lymphocyte numbers in the F2 female rats fed the LO-20% diet compared to those fed the LH-20% fish diet. These results suggested that long-term exposure to Great Lakes fish contaminants may have adverse effects on some immune-related parameters. The impact of such changes on the functional aspects of the immune system of rats and consequently on human health needs to be further investigated.

Animal Feed↗
PubMed1998

Effects of Great Lakes fish consumption on the immune system of Sprague-Dawley rats investigated during a two-generation reproductive study.

The effects of Great Lakes fish contaminants on several quantitative and functional aspects of the immune system were investigated in the first (F1) and second (F2) generations of Sprague-Dawley rats. The F0 rats were fed either a control diet or diets containing 5 or 20% lyophilized chinook salmon from the Credit River of Lake Ontario (LO) and Owen Sound point of Lake Huron (LH). The F1 and F2 pups were exposed to fish in utero, through the dam's milk to 21 days old, and through the dam's respective diets to 13 weeks of age. The study included an F1-reversibility (F1-R) phase in which rats at 13 weeks of exposure to fish or control diets were switched to the control diet for 3 months. The most outstanding finding was a statistically significant increase in absolute spleen leukocytes and absolute and percentage lymphocytes in the F2 male rats fed the LH fish diets compared to the control and to those fed the LO fish diets with the 20% fish diets having higher cell numbers compared to the LO-5% fish diets. A parallel increase in the T-helper/inducer T-lymphocyte subset numbers was observed. Increased but statistically insignificant plaque-forming cell (PFC) numbers were obtained in the F2 male rats fed the LH fish diets compared to those fed the LO fish diets and in the F1-R female group of rats fed the LH fish diet compared to those fed the LO fish diets. Phagocytosis by resident peritoneal macrophages was significantly increased in the F1 male and F2 female rats fed the fish diets compared to the control. The phagocytic activity was significantly higher in the F2-generation male and female rats fed the LO diets compared to those fed the LH diets. Other parameters including lymphocyte transformation in response to mitogens, the number of Listeria monocytogenes bacteria surviving in the rat spleens, and the natural killer cell activity were not affected significantly by any of the treatments. Overall, the effects of diets containing chinook salmon from the LO and LH sources on the immune system of rats were minimal and were on quantitative rather than on functional aspects of the system. Further focused research would be required in order to establish conclusively that the immune system of cohorts who ingest Great Lakes fish frequently is at a greater risk for adverse effects.

Animal Feed↗
PubMed1996

Germline BRCA1 185delAG mutations in Jewish women with breast cancer.

BACKGROUND: We aimed to find out the proportion of breast cancers in Ashkenazi Jewish women attributable to the frameshift mutation at position 185 involving the deletion of adenine and guanine (185delAG) in the breast cancer gene BRCA1. METHODS: We studied 107 Ashkenazi Jewish women with breast cancer seen at medical oncology and genetic counseling clinics in New York over a three and a half year period beginning in 1992. 80 of the women were diagnosed before age 42 years; the other 27 were diagnosed between 42 and 50 years and had a positive family history. Genomic DNA testing by PCR amplification was done to identify any 185delAG mutations of the BRCA1 gene. FINDINGS: Of the 80 women diagnosed before the age of 42 years, 16 (20%, 95% CI 11.2-28.8) were heterozygous for the mutation. All 16 women had at least one first-degree or second-degree relative with breast or ovarian cancer. Of 27 probands diagnosed with breast cancer between the ages of 42 and 50 years who had at least one first-degree relative affected with breast or ovarian cancer, 8 (30%, 95% CI 12-47) had 185delAG mutations. INTERPRETATION: These data suggest that screening for the 185delAG mutation may be useful in genetic counselling of these women where options for detection and prevention of possible cancers can be discussed.

Adult↗
PubMed1996

Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer.

The lifetime risk of breast cancer may approach 80-90% in women who have germline mutations of either of two genes, BRCA1 or BRCA2. A single BRCA1 mutation, 185delAG, has been noted in approximately 20% of Ashkenazi Jewish women with early onset breast cancer and in 0.9% of the Ashkenazi population. We recently detected a 6174delT frameshift mutation in BRCA2 in an hereditary breast cancer kindred of Ashkenazi Jewish ancestry. Here, we investigated the frequency of this mutation in 200 women with early-onset breast cancer. Six of 80 Ashkenazi Jewish women (8%) diagnosed with breast cancer before the age of 42, wer heterozygous for the 6174delT mutation, compared to none of 93 non-Jewish women diagnosed with breast cancer at the same age (P = .005). These cases were ascertained without regard to family history. Two of 27 (7%) additional Jewish families in which the proband was diagnosed with breast cancer at age 42 to 50 and had a family history of breast or ovarian cancer had germline 6174delT mutations. The results of this report suggest that a recurrent mutation of BRCA1 and a recurrent mutation BRCA2 together may account for over a quarter of all early-onset breast cancer in the setting of a personal or family history of ovarian cancer in Ashkenazi Jewish women.

Adult↗