Large-Scale Networks for Auditory Sensory Gating in the Awake Mouse

The amplitude of the brain response to a repeated auditory stimulus is diminished as compared to the response to the first tone (T1) for interstimulus intervals (ISI) lasting up to hundreds of milliseconds. This adaptation process, called auditory sensory gating (ASG), is altered in various psychiatric diseases including schizophrenia and is classically studied by focusing on early evoked cortical responses to the second tone (T2) using 500-ms ISI. However, mechanisms underlying ASG are still not well-understood. We investigated ASG in awake mice from the brainstem to cortex at variable ISIs (125-2000 ms) using high-density EEG and intracerebral recordings. While ASG decreases at longer ISIs, it is still present at durations (500-2000 ms) far beyond the time during which brain responses to T1 could still be detected. T1 induces a sequence of specific stable scalp EEG topographies that correspond to the successive activation of distinct neural networks lasting about 350 ms. These brain states remain unaltered if T2 is presented during this period, although T2 is processed by the brain, suggesting that ongoing networks of brain activity are active for longer than early evoked-potentials and are not overwritten by an upcoming new stimulus. Intracerebral recordings demonstrate that ASG is already present at the level of ventral cochlear nucleus (vCN) and inferior colliculus and is amplified across the hierarchy in bottom-up direction. This study uncovers the extended stability of sensory-evoked brain states and long duration of ASG, and sheds light on generators of ASG and possible interactions between bottom-up and top-down mechanisms

Distant heterotopic callosal connections to premotor cortex in non-human primates

Cortico-cortical connectivity has become a major focus of neuroscience in the last decade but most of the connectivity studies focused on intrahemispheric circuits. Little has been reported about information acquired and processed in the premotor cortex and its functional connection with its homotopic counterpart in the opposite hemisphere via the corpus callosum. In non-human primates (macaques) lateralization is not well documented and its exact role is still unknown. The present study confirms in two macaques the existence of homotopic contralateral projections and completes the picture by further exploring heterotopic (non-motor) callosal projections. This was tested by injecting retrograde tracers in the premotor cortical areas PMv and PMd (targets). Our method consisted of identifying the connections with all the homo- and heterotopic cortical areas located in the contralateral hemisphere. The results showed that PMd and PMv receive multiple low-density labeled inputs from the opposite heterotopic prefrontal, parietal, motor, insular and temporal regions. Such unexpected collection of transcallosal inputs from heterotopic areas suggests that the premotor areas communicate with other modalities through long distance low-density networks which could have important implications in the understanding of sensorimotor and multimodal integration

Free Breathing Real-Time Cardiac Cine Imaging With Improved Spatial Resolution at 3 T

Objectives: The aim of this study was to evaluate free-breathing single-shot real-time cine imaging for functional cardiac imaging at 3 +/- with increased spatial resolution. Special emphasis of this study was placed on the influence of parallel imaging techniques. Materials and Methods: Gradient echo phantom images were acquired with GRAPPA and modified SENSE reconstruction using both integrated and separate reference scans as well as TGRAPPA and TSENSE. In vivo measurements were performed for GRAPPA reconstruction with an integrated and a separate reference scan, as well as TGRAPPA using balanced steady-state free precession protocols. Three clinical protocols, rtLRInt (T-res = 51.3 milliseconds; voxel, 2.5 x 5.0 x 10 mm(3)), rtMRSep (T-res = 48.8 milliseconds; voxel, 1.9 x 3.1 x 10 mm(3)), and rtHRSep ((Tres) = 48.3 milliseconds; voxel, 1.6 x 2.6 x 10 mm(3)), were investigated on 20 volunteers using GRAPPA reconstruction with internal as well as separate reference scans. End-diastolic volume, end-systolic volume, ejection fraction, peak ejection rate, peak filling rate, and myocardial mass were evaluated for the left ventricle and compared with an electrocardiogram-triggered segmented readout cine protocol used as standard of reference. All studies were performed at 3 T. Results: Phantom and in vivo data demonstrate that the combination of GRAPPA reconstruction with a separate reference scan provides an optimal compromise of image quality as well as spatial and temporal resolution. Functional values (P values) for the standard of reference, rtLRInt, rtMRSep, and rtHRSep end-diastolic volume were 141 +/- 24 mL, 138 +/- 21 mL, 138 +/- 19 mL, and 128 +/- 33 mL, respectively (P = 0.7, 0.7, 0.4); end-systolic volume, 55 +/- 15 mL, 61 +/- 14 mL, 58 +/- 12 mL, and 55 +/- 20 mL, respectively (P = 0.23, 0.43, 0.62); ejection fraction, 61% +/- 5%, 57% +/- 5%, 58% +/- 4%, and 56% +/- 8%, respectively (P = 0.01, 0.11, 0.06); peak ejection rate, 481 +/- 73 mL/s, 425 +/- 62 mL/s, 434 +/- 67 mL/s, and 381 +/- 86 mL/s, respectively (P = 0.03, 0.04, 0.01); peak filling rate, 555 +/- 80 mL/s, 480 +/- 70 mL/s, 500 +/- 70 mL/s, and 438 +/- 108 mL/s, respectively (P = 0.007, 0.05, 0.004); and myocardial mass, 137 +/- 26 g, 141 T 25 g, 141 +/- 23 g, and 130 +/- 31 g, respectively (P = 0.62, 0.54, 0.99). Conclusions: Using a separate reference scan and high acceleration factors up to R = 6, single-shot real-time cardiac imaging offers adequate temporal and spatial resolution for accurate assessment of global left ventricular function in free breathing with short examination times

Free Breathing Real-Time Cardiac Cine Imaging With Improved Spatial Resolution at 3 T

Objectives: The aim of this study was to evaluate free-breathing single-shot real-time cine imaging for functional cardiac imaging at 3 +/- with increased spatial resolution. Special emphasis of this study was placed on the influence of parallel imaging techniques. Materials and Methods: Gradient echo phantom images were acquired with GRAPPA and modified SENSE reconstruction using both integrated and separate reference scans as well as TGRAPPA and TSENSE. In vivo measurements were performed for GRAPPA reconstruction with an integrated and a separate reference scan, as well as TGRAPPA using balanced steady-state free precession protocols. Three clinical protocols, rtLRInt (T-res = 51.3 milliseconds; voxel, 2.5 x 5.0 x 10 mm(3)), rtMRSep (T-res = 48.8 milliseconds; voxel, 1.9 x 3.1 x 10 mm(3)), and rtHRSep ((Tres) = 48.3 milliseconds; voxel, 1.6 x 2.6 x 10 mm(3)), were investigated on 20 volunteers using GRAPPA reconstruction with internal as well as separate reference scans. End-diastolic volume, end-systolic volume, ejection fraction, peak ejection rate, peak filling rate, and myocardial mass were evaluated for the left ventricle and compared with an electrocardiogram-triggered segmented readout cine protocol used as standard of reference. All studies were performed at 3 T. Results: Phantom and in vivo data demonstrate that the combination of GRAPPA reconstruction with a separate reference scan provides an optimal compromise of image quality as well as spatial and temporal resolution. Functional values (P values) for the standard of reference, rtLRInt, rtMRSep, and rtHRSep end-diastolic volume were 141 +/- 24 mL, 138 +/- 21 mL, 138 +/- 19 mL, and 128 +/- 33 mL, respectively (P = 0.7, 0.7, 0.4); end-systolic volume, 55 +/- 15 mL, 61 +/- 14 mL, 58 +/- 12 mL, and 55 +/- 20 mL, respectively (P = 0.23, 0.43, 0.62); ejection fraction, 61% +/- 5%, 57% +/- 5%, 58% +/- 4%, and 56% +/- 8%, respectively (P = 0.01, 0.11, 0.06); peak ejection rate, 481 +/- 73 mL/s, 425 +/- 62 mL/s, 434 +/- 67 mL/s, and 381 +/- 86 mL/s, respectively (P = 0.03, 0.04, 0.01); peak filling rate, 555 +/- 80 mL/s, 480 +/- 70 mL/s, 500 +/- 70 mL/s, and 438 +/- 108 mL/s, respectively (P = 0.007, 0.05, 0.004); and myocardial mass, 137 +/- 26 g, 141 T 25 g, 141 +/- 23 g, and 130 +/- 31 g, respectively (P = 0.62, 0.54, 0.99). Conclusions: Using a separate reference scan and high acceleration factors up to R = 6, single-shot real-time cardiac imaging offers adequate temporal and spatial resolution for accurate assessment of global left ventricular function in free breathing with short examination times

The M235T Polymorphism in the AGT Gene and CHD Risk: Evidence of a Hardy-Weinberg Equilibrium Violation and Publication Bias in a Meta-Analysis

BACKGROUND: The M235T polymorphism in the AGT gene has been related to an increased risk of hypertension. This finding may also suggest an increased risk of coronary heart disease (CHD). METHODOLOGY/PRINCIPAL FINDINGS: A case-cohort study was conducted in 1,732 unrelated middle-age women (210 CHD cases and 1,522 controls) from a prospective cohort of 15,236 initially healthy Dutch women. We applied a Cox proportional hazards model to study the association of the polymorphism with acute myocardial infarction (AMI) (n = 71) and CHD. In the case-cohort study, no increased risk for CHD was found under the additive genetic model (hazard ratio [HR] = 1.20; 95% confidence interval [CI], 0.86 to 1.68; P = 0.28). This result was not changed by adjustment (HR = 1.17; 95% CI, 0.83 to 1.64; P = 0.38) nor by using dominant, recessive and pairwise genetic models. Analyses for AMI risk under the additive genetic model also did not show any statistically significant association (crude HR = 1.14; 95% CI, 0.93 to 1.39; P = 0.20). To evaluate the association, a comprehensive systematic review and meta-analysis were undertaken of all studies published up to February 2007 (searched through PubMed/MEDLINE, Web of Science and EMBASE). The meta-analysis (38 studies with 13284 cases and 18722 controls) showed a per-allele odds ratio (OR) of 1.08 (95% CI, 1.01 to 1.15; P = 0.02). Moderate to large levels of heterogeneity were identified between studies. Hardy-Weinberg equilibrium (HWE) violation and the mean age of cases were statistically significant sources of the observed variation. In a stratum of non-HWE violation studies, there was no effect. An asymmetric funnel plot, the Egger's test (P = 0.066), and the Begg-Mazumdar test (P = 0.074) were all suggestive of the presence of publication bias. CONCLUSIONS/SIGNIFICANCE: The pooled OR of the present meta-analysis, including our own data, presented evidence that there is an increase in the risk of CHD conferred by the M235T variant of the AGT gene. However, the relevance of this weakly positive overall association remains uncertain because it may be due to various residual biases, including HWE-violation and publication biases

Whole-scalp EEG mapping of somatosensory evoked potentials in macaque monkeys

High-density scalp EEG recordings are widely used to study whole-brain neuronal networks in humans non-invasively. Here, we validate EEG mapping of somatosensory evoked potentials (SSEPs) in macaque monkeys (Macaca fascicularis) for the long-term investigation of large-scale neuronal networks and their reorganisation after lesions requiring a craniotomy. SSEPs were acquired from 33 scalp electrodes in five adult anaesthetized animals after electrical median or tibial nerve stimulation. SSEP scalp potential maps were identified by cluster analysis and identified in individual recordings. A distributed, linear inverse solution was used to estimate the intracortical sources of the scalp potentials. SSEPs were characterised by a sequence of components with unique scalp topographies. Source analysis confirmed that median nerve SSEP component maps were in accordance with the somatotopic organisation of the sensorimotor cortex. Most importantly, SSEP recordings were stable both intra- and interindividually. We aim to apply this method to the study of recovery and reorganisation of large-scale neuronal networks following a focal cortical lesion requiring a craniotomy. As a prerequisite, the present study demonstrated that a 300-mm2 unilateral craniotomy over the sensorimotor cortex necessary to induce a cortical lesion, followed by bone flap repositioning, suture and gap plugging with calcium phosphate cement, did not induce major distortions of the SSEPs. In conclusion, SSEPs can be successfully and reproducibly recorded from high-density EEG caps in macaque monkeys before and after a craniotomy, opening new possibilities for the long-term follow-up of the cortical reorganisation of large-scale networks in macaque monkeys after a cortical lesion

Refined methodology for implantation of a head fixation device and chronic recording chambers in non-human primates

The present study was aimed at developing a new strategy to design and anchor custom-fitted implants, consisting of a head fixation device and a chronic recording chamber, on the skull of adult macaque monkeys. This was done without the use of dental resin or orthopedic cement, as these modes of fixation exert a detrimental effect on the bone. The implants were made of titanium or tekapeek and anchored to the skull with titanium screws. Two adult macaque monkeys were initially implanted with the head fixation device several months previous to electrophysiological investigation, to allow optimal osseous-integration, including growth of the bone above the implant's footplate. In a second step, the chronic recording chamber was implanted above the brain region of interest. The present study proposes two original approaches for both implants. First, based on a CT scan of the monkey, a plastic replicate of the skull was obtained in the form of a 3D print, used to accurately shape and position the two implants. This would ensure a perfect match with the skull surface. Second, the part of the implants in contact with the bone was coated with hydroxyapatite, presenting chemical similarity to natural bone, thus promoting excellent osseous-integration. The longevity of the implants used here was 4 years for the head fixation device and 1.5 years for the chronic chamber. There were no adverse events and daily care was easy. This is clear evidence that the present implanting strategy was successful and provokes less discomfort to the animals