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Michelle Moody

Publications and source records attributed to Michelle Moody.

4 recordsLinked to original sources

Cerebral blood flow velocity during mental activation: interpretation with different models of the passive pressure-velocity relationship.

The passive relationship between arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) has been expressed by a single parameter [cerebrovascular resistance (CVR)] or, alternatively, by a two-parameter model, comprising a resistance element [resistance-area product (RAP)] and a critical closing pressure (CrCP). We tested the hypothesis that the RAP+CrCP model can provide a more consistent interpretation to CBFV responses induced by mental activation tasks than the CVR model. Continuous recordings of CBFV [bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal CO(2) (EtCO(2)) were performed in 13 right-handed healthy subjects (aged 21-43 yr), in the seated position, at rest and during 10 repeated presentations of a word generation and a constructional puzzle paradigm that are known to induce differential cortical activation. Due to its small relative change, the CBFV response can be broken down into standardized subcomponents describing the relative contributions of ABP, CVR, RAP, and CrCP. At rest and during activation, the RAP+CrCP model suggested that RAP might reflect myogenic activity in response to the ABP transient, whereas CrCP was more indicative of metabolic control. These different influences were not reflected by the CVR model, which indicated a predominantly metabolic response. Repeated-measures multi-way ANOVA showed that CrCP (P = 0.025), RAP (P = 0.046), and CVR (P = 0.002) changed significantly during activation. CrCP also had a significant effect of paradigm (P = 0.045) but not hemispheric dominance. Both RAP (P = 0.039) and CVR (P = 0.0008) had significant effects of hemispheric dominance but were not sensitive to the different paradigms. Subcomponent analysis can help with the interpretation of CBFV responses to mental activation, which were found to be dependent on the underlying model of the passive ABP-CBFV relationship.

Adult↗

Dynamic cerebral autoregulation during brain activation paradigms.

Dynamic cerebral autoregulation (CA) describes the transient response of cerebral blood flow (CBF) to rapid changes in arterial blood pressure (ABP). We tested the hypothesis that the efficiency of dynamic CA is increased by brain activation paradigms designed to induce hemispheric lateralization. CBF velocity [CBFV; bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal Pco(2) were continuously recorded in 14 right-handed healthy subjects (21-43 yr of age), in the seated position, at rest and during 10 repeated presentations (30 s on-off) of a word generation test and a constructional puzzle. Nonstationarities were not found during rest or activation. Transfer function analysis of the ABP-CBFV (i.e., input-output) relation was performed for the 10 separate 51.2-s segments of data during activation and compared with baseline data. During activation, the coherence function below 0.05 Hz was significantly increased for the right MCA recordings for the puzzle tasks compared with baseline values (0.36 +/- 0.16 vs. 0.26 +/- 0.13, P < 0.05) and for the left MCA recordings for the word paradigm (0.48 +/- 0.23 vs. 0.29 +/- 0.16, P < 0.05). In the same frequency range, significant increases in gain were observed during the puzzle paradigm for the right (0.69 +/- 0.37 vs. 0.46 +/- 0.32 cm.s(-1).mmHg(-1), P < 0.05) and left (0.61 +/- 0.29 vs. 0.45 +/- 0.24 cm.s(-1).mmHg(-1), P < 0.05) hemispheres and during the word tasks for the left hemisphere (0.66 +/- 0.31 vs. 0.39 +/- 0.15 cm.s(-1).mmHg(-1), P < 0.01). Significant reductions in phase were observed during activation with the puzzle task for the right (-0.04 +/- 1.01 vs. 0.80 +/- 0.86 rad, P < 0.01) and left (0.11 +/- 0.81 vs. 0.57 +/- 0.51 rad, P < 0.05) hemispheres and with the word paradigm for the right hemisphere (0.05 +/- 0.87 vs. 0.64 +/- 0.59 rad, P < 0.05). Brain activation also led to changes in the temporal pattern of the CBFV step response. We conclude that transfer function analysis suggests important changes in dynamic CA during mental activation tasks.

Adult↗

Cerebral and systemic hemodynamic changes during cognitive and motor activation paradigms.

Cognitive and/or sensorimotor stimulations of the brain induce increases in cerebral blood flow that are usually associated with increased metabolic demand. We tested the hypothesis that changes in arterial blood pressure (ABP) and arterial Pco(2) also take place during brain activation protocols designed to induce hemispheric lateralization, leading to a pressure-autoregulatory response in addition to the metabolic-driven changes usually assumed by brain stimulation paradigms. Continuous recordings of cerebral blood flow velocity [CBFV; bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal Pco(2) (Pet(CO(2))) were performed in 15 right-handed healthy subjects (aged 21-43 yr), in the seated position, at rest and during 10 repeated presentations of a word generation and a constructional puzzle paradigm that are known to induce differential cortical activation. Derived variables included heart rate, cerebrovascular resistance, critical closing pressure, resistance area product, and the difference between the right and left MCA recordings (CBFV(R-L)). No adaptation of the CBFV(R-L) difference was detected for the repeated presentation of 10 activation tasks, for either paradigm. During activation with the word generation tasks, CBFV changed by (mean +/- SD) 9.0 +/- 3.7% (right MCA, P = 0.0007) and by 12.3 +/- 7.6% (left MCA, P = 0.0007), ABP by 7.7 +/- 6.0 mmHg (P = 0.0007), heart rate by 7.1 +/- 5.3 beats/min (P = 0.0008), and Pet(CO(2)) by -2.32 +/- 2.23 Torr (P = 0.002). For the puzzle paradigm, CBFV changed by 13.9 +/- 6.6% (right MCA, P = 0.0007) and by 11.5 +/- 6.2% (left MCA, P = 0.0007), ABP by 7.1 +/- 8.4 mmHg (P = 0.0054), heart rate by 7.9 +/- 4.6 beats/min (P = 0.0008), and Pet(CO(2)) by -2.42 +/- 2.59 Torr (P = 0.001). The word paradigm led to greater left hemispheric dominance than the right hemispheric dominance observed with the puzzle paradigm (P = 0.004). We concluded that significant changes in ABP and Pet(CO(2)) levels occur during brain activation protocols, and these contribute to the evoked change in CBFV. A pressure-autoregulatory response can be observed in addition to the hemodynamic changes induced by increases in metabolic demand. Simultaneous changes in Pco(2) and heart rate add to the complexity of the response, indicating the need for more detailed modeling and better understanding of brain activation paradigms.

Adult↗

A P-element insertion screen identified mutations in 455 novel essential genes in Drosophila.

With the completion of the nucleotide sequences of several complex eukaryotic genomes, tens of thousands of genes have been predicted. However, this information has to be correlated with the functions of those genes to enhance our understanding of biology and to improve human health care. The Drosophila transposon P-element-induced mutations are very useful for directly connecting gene products to their biological function. We designed an efficient transposon P-element-mediated gene disruption procedure and performed genetic screening for single P-element insertion mutations, enabling us to recover 2500 lethal mutations. Among these, 2355 are second chromosome mutations. Sequences flanking >2300 insertions that identify 850 different genes or ESTs (783 genes on the second chromosome and 67 genes on the third chromosome) have been determined. Among these, 455 correspond to genes for which no lethal mutation has yet been reported. The Drosophila genome is thought to contain approximately 3600 vital genes; 1400 are localized on the second chromosome. Our mutation collection represents approximately 56% of the second chromosome vital genes and approximately 24% of the total vital Drosophila genes.

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