Long-term stability of adipose tissue generated from a vascularized pedicled fat flap inside a chamber

Background Numerous studies demonstrate the generation and short-term survival of adipose tissue; however, long-term persistence remains elusive. This study evaluates long-term survival and transferability of de novo adipose constructs based on a ligated vascular pedicle and tissue engineering chamber combination. Methods Defined adipose tissue flaps were implanted into rats in either intact or perforated domed chambers. In half of the groups, the chambers were removed after 10 weeks and the constructs transferred on their vascular pedicle to a new site, where they were observed for a further 10 weeks. In the remaining groups, the tissue construct was observed for 20 weeks inside the chamber. Tissue volume was assessed using magnetic resonance imaging and histologic measures, and constructs were assessed for stability and necrosis. Sections were assessed histologically and for proliferation using Ki-67. Results At 20 weeks, volume analysis revealed an increase in adipose volume from 0.04 ± 0.001 ml at the time of insertion into the chambers to 0.27 ± 0.004 ml in the closed and 0.44 ± 0.014 ml in the perforated chambers. There was an additional increase of approximately 10 to 15 percent in tissue volume in flaps that remained in chambers for 20 weeks, whereas the volume of the transferred tissue not in chambers remained unaltered. Histomorphometric assessment of the tissues documented no signs of hypertrophy, fat necrosis, or atypical changes of the newly generated tissue. Conclusion This study presents a promising new method of generating significant amounts of mature, vascularized, stable, and transferable adipose tissue for permanent autologous soft-tissue replacement.

Characterisation of the micro-architecture of direct writing melt electrospun tissue engineering scaffolds using diffusion tensor and computed tomography microimaging

This article describes the first steps toward comprehensive characterization of molecular transport within scaffolds for tissue engineering. The scaffolds were fabricated using a novel melt electrospinning technique capable of constructing 3D lattices of layered polymer fibers with well - defined internal microarchitectures. The general morphology and structure order was then determined using T 2 - weighted magnetic resonance imaging and X - ray microcomputed tomography. Diffusion tensor microimaging was used to measure the time - dependent diffusivity and diffusion anisotropy within the scaffolds. The measured diffusion tensors were anisotropic and consistent with the cross - hatched geometry of the scaffolds: diffusion was least restricted in the direction perpendicular to the fiber layers. The results demonstrate that the cross - hatched scaffold structure preferentially promotes molecular transport vertically through the layers ( z - axis), with more restricted diffusion in the directions of the fiber layers ( x – y plane). Diffusivity in the x – y plane was observed to be invariant to the fiber thickness. The characteristic pore size of the fiber scaffolds can be probed by sampling the diffusion tensor at multiple diffusion times. Prospective application of diffusion tensor imaging for the real - time monitoring of tissue maturation and nutrient transport pathways within tissue engineering scaffolds is discussed.

Made-to-order nanocarbons through deterministic plasma nanotechnology

Through a combinatorial approach involving experimental measurement and plasma modelling, it is shown that a high degree of control over diamond-like nanocarbon film sp3/sp2 ratio (and hence film properties) may be exercised, starting at the level of electrons (through modification of the plasma electron energy distribution function). Hydrogenated amorphous carbon nanoparticle films with high percentages of diamond-like bonds are grown using a middle-frequency (2 MHz) inductively coupled Ar + CH4 plasma. The sp3 fractions measured by X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy in the thin films are explained qualitatively using sp3/sp2 ratios 1) derived from calculated sp3 and sp2 hybridized precursor species densities in a global plasma discharge model and 2) measured experimentally. It is shown that at high discharge power and lower CH4 concentrations, the sp3/sp2 fraction is higher. Our results suggest that a combination of predictive modeling and experimental studies is instrumental to achieve deterministically grown made-to-order diamond-like nanocarbons suitable for a variety of applications spanning from nano-magnetic resonance imaging to spin-flip quantum information devices. This deterministic approach can be extended to graphene, carbon nanotips, nanodiamond and other nanocarbon materials for a variety of applications

Dopamine transporter genotype predicts behavioural and neural measures of response inhibition

The ability to inhibit unwanted actions is a heritable executive function that may confer risk to disorders such as attention deficit hyperactivity disorder (ADHD). Converging evidence from pharmacology and cognitive neuroscience suggests that response inhibition is instantiated within frontostriatal circuits of the brain with patterns of activity that are modulated by the catecholamines dopamine and noradrenaline. A total of 405 healthy adult participants performed the stop-signal task, a paradigmatic measure of response inhibition that yields an index of the latency of inhibition, termed the stop-signal reaction time (SSRT). Using this phenotype, we tested for genetic association, performing high-density single-nucleotide polymorphism mapping across the full range of autosomal catecholamine genes. Fifty participants also underwent functional magnetic resonance imaging to establish the impact of associated alleles on brain and behaviour. Allelic variation in polymorphisms of the dopamine transporter gene (SLC6A3: rs37020; rs460000) predicted individual differences in SSRT, after corrections for multiple comparisons. Furthermore, activity in frontal regions (anterior frontal, superior frontal and superior medial gyri) and caudate varied additively with the T-allele of rs37020. The influence of genetic variation in SLC6A3 on the development of frontostriatal inhibition networks may represent a key risk mechanism for disorders of behavioural inhibition.

Semantic context and visual feature effects in object naming : an fMRI study using arterial spin labeling

Previous behavioral studies reported a robust effect of increased naming latencies when objects to be named were blocked within semantic category, compared to items blocked between category. This semantic context effect has been attributed to various mechanisms including inhibition or excitation of lexico-semantic representations and incremental learning of associations between semantic features and names, and is hypothesized to increase demands on verbal self-monitoring during speech production. Objects within categories also share many visual structural features, introducing a potential confound when interpreting the level at which the context effect might occur. Consistent with previous findings, we report a significant increase in response latencies when naming categorically related objects within blocks, an effect associated with increased perfusion fMRI signal bilaterally in the hippocampus and in the left middle to posterior superior temporal cortex. No perfusion changes were observed in the middle section of the left middle temporal cortex, a region associated with retrieval of lexical-semantic information in previous object naming studies. Although a manipulation of visual feature similarity did not influence naming latencies, we observed perfusion increases in the perirhinal cortex for naming objects with similar visual features that interacted with the semantic context in which objects were named. These results provide support for the view that the semantic context effect in object naming occurs due to an incremental learning mechanism, and involves increased demands on verbal self-monitoring.

Dissociating verbal and nonverbal audiovisual object processing

This fMRI study investigates how audiovisual integration differs for verbal stimuli that can be matched at a phonological level and nonverbal stimuli that can be matched at a semantic level. Subjects were presented simultaneously with one visual and one auditory stimulus and were instructed to decide whether these stimuli referred to the same object or not. Verbal stimuli were simultaneously presented spoken and written object names, and nonverbal stimuli were photographs of objects simultaneously presented with naturally occurring object sounds. Stimulus differences were controlled by including two further conditions that paired photographs of objects with spoken words and object sounds with written words. Verbal matching, relative to all other conditions, increased activation in a region of the left superior temporal sulcus that has previously been associated with phonological processing. Nonverbal matching, relative to all other conditions, increased activation in a right fusiform region that has previously been associated with structural and conceptual object processing. Thus, we demonstrate how brain activation for audiovisual integration depends on the verbal content of the stimuli, even when stimulus and task processing differences are controlled.

Integrating visual and tactile information in the perirhinal cortex

By virtue of its widespread afferent projections, perirhinal cortex is thought to bind polymodal information into abstract object-level representations. Consistent with this proposal, deficits in cross-modal integration have been reported after perirhinal lesions in nonhuman primates. It is therefore surprising that imaging studies of humans have not observed perirhinal activation during visual-tactile object matching. Critically, however, these studies did not differentiate between congruent and incongruent trials. This is important because successful integration can only occur when polymodal information indicates a single object (congruent) rather than different objects (incongruent). We scanned neurologically intact individuals using functional magnetic resonance imaging (fMRI) while they matched shapes. We found higher perirhinal activation bilaterally for cross-modal (visual-tactile) than unimodal (visual-visual or tactile-tactile) matching, but only when visual and tactile attributes were congruent. Our results demonstrate that the human perirhinal cortex is involved in cross-modal, visual-tactile, integration and, thus, indicate a functional homology between human and monkey perirhinal cortices.

The effect of prior visual information on recognition of speech and sounds

To identify and categorize complex stimuli such as familiar objects or speech, the human brain integrates information that is abstracted at multiple levels from its sensory inputs. Using cross-modal priming for spoken words and sounds, this functional magnetic resonance imaging study identified 3 distinct classes of visuoauditory incongruency effects: visuoauditory incongruency effects were selective for 1) spoken words in the left superior temporal sulcus (STS), 2) environmental sounds in the left angular gyrus (AG), and 3) both words and sounds in the lateral and medial prefrontal cortices (IFS/mPFC). From a cognitive perspective, these incongruency effects suggest that prior visual information influences the neural processes underlying speech and sound recognition at multiple levels, with the STS being involved in phonological, AG in semantic, and mPFC/IFS in higher conceptual processing. In terms of neural mechanisms, effective connectivity analyses (dynamic causal modeling) suggest that these incongruency effects may emerge via greater bottom-up effects from early auditory regions to intermediate multisensory integration areas (i.e., STS and AG). This is consistent with a predictive coding perspective on hierarchical Bayesian inference in the cortex where the domain of the prediction error (phonological vs. semantic) determines its regional expression (middle temporal gyrus/STS vs. AG/intraparietal sulcus).

Comparison of block and event-related experimental designs in diffusion-weighted functional MRI

PURPOSE To compare diffusion-weighted functional magnetic resonance imaging (DfMRI), a novel alternative to the blood oxygenation level-dependent (BOLD) contrast, in a functional MRI experiment. MATERIALS AND METHODS Nine participants viewed contrast reversing (7.5 Hz) black-and-white checkerboard stimuli using block and event-related paradigms. DfMRI (b = 1800 mm/s2 ) and BOLD sequences were acquired. Four parameters describing the observed signal were assessed: percent signal change, spatial extent of the activation, the Euclidean distance between peak voxel locations, and the time-to-peak of the best fitting impulse response for different paradigms and sequences. RESULTS The BOLD conditions showed a higher percent signal change relative to DfMRI; however, event-related DfMRI showed the strongest group activation (t = 21.23, P < 0.0005). Activation was more diffuse and spatially closer to the BOLD response for DfMRI when the block design was used. DfMRIevent showed the shortest TTP (4.4 +/- 0.88 sec). CONCLUSION The hemodynamic contribution to DfMRI may increase with the use of block designs.

Metal artifacts from titanium and steel screws in CT, 1.5T and 3T MR images of the tibial Pilon: A quantitative assessment in 3D

Radiographs are commonly used to assess articular reduction of the distal tibia (pilon) fractures postoperatively, but may reveal malreductions inaccurately. While Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) are potential 3D alternatives they generate metal-related artifacts. This study aims to quantify the artifact size from orthopaedic screws using CT, 1.5T and 3T MRI data. Three screws were inserted into one intact human cadaver ankle specimen proximal to and along the distal articular surface, then CT, 1.5T and 3T MRI scanned. Four types of screws were investigated: titanium alloy (TA), stainless steel (SS) (Ø = 3.5 mm), cannulated TA (CTA) and cannulated SS (CSS)(Ø = 4.0 mm, Ø empty core = 2.6 mm). 3D artifact models were reconstructed using adaptive thresholding. The artifact size was measured by calculating the perpendicular distance from the central screw axis to the boundary of the artifact in four anatomical directions with respect to the distal tibia. The artifact sizes (in the order of TA, SS, CTA and CSS) from CT were 2.0 mm, 2.6 mm, 1.6 mm and 2.0 mm; from 1.5T MRI they were 3.7 mm, 10.9 mm, 2.9 mm, and 9 mm; and 3T MRI they were 4.4 mm, 15.3 mm, 3.8 mm, and 11.6 mm respectively. Therefore, CT can be used as long as the screws are at a safe distance of about 2 mm from the articular surface. MRI can be used if the screws are at least 3 mm away from the articular surface except SS and CSS. Artifacts from steel screws were too large thus obstructed the pilon from being visualised in MRI. Significant differences (P < 0.05) were found in the size of artifacts between all imaging modalities, screw types and material types, except 1.5T versus 3T MRI for the SS screws (P = 0.063). CTA screws near the joint surface can improve postoperative assessment in CT and MRI. MRI presents a favourable non-ionising alternative when using titanium hardware. Since these factors may influence the quality of postoperative assessment, potential improvements in operative techniques should be considered.

Stop-signal task difficulty and the right inferior frontal gyrus

The stop-signal paradigm is increasingly being used as a probe of response inhibition in basic and clinical neuroimaging research. The critical feature of this task is that a cued response is countermanded by a secondary ‘stop-signal’ stimulus offset from the first by a ‘stop-signal delay’. Here we explored the role of task difficulty in the stop-signal task with the hypothesis that what is critical for successful inhibition is the time available for stopping, that we define as the difference between stop-signal onset and the expected response time (approximated by reaction time from previous trial). We also used functional magnetic resonance imaging (fMRI) to examine how the time available for stopping affects activity in the putative right inferior frontal gyrus and presupplementary motor area (right IFG-preSMA) network that is known to support stopping. While undergoing fMRI scanning, participants performed a stop-signal variant where the time available for stopping was kept approximately constant across participants, which enabled us to compare how the time available for stopping affected stop-signal task difficulty both within and between subjects. Importantly, all behavioural and neuroimaging data were consistent with previous findings. We found that the time available for stopping distinguished successful from unsuccessful inhibition trials, was independent of stop-signal delay, and affected successful inhibition depending upon individual SSRT. We also found that right IFG and adjacent anterior insula were more strongly activated during more difficult stopping. These findings may have critical implications for stop-signal studies that compare different patient or other groups using fixed stop-signal delays.

Brain networks subserving the evaluation of static and dynamic facial expressions

Because moving depictions of face emotion have greater ecological validity than their static counterparts, it has been suggested that still photographs may not engage ‘authentic’ mechanisms used to recognize facial expressions in everyday life. To date, however, no neuroimaging studies have adequately addressed the question of whether the processing of static and dynamic expressions rely upon different brain substrates. To address this, we performed an functional magnetic resonance imaging (fMRI) experiment wherein participants made emotional expression discrimination and Sex discrimination judgements to static and moving face images. Compared to Sex discrimination, Emotion discrimination was associated with widespread increased activation in regions of occipito-temporal, parietal and frontal cortex. These regions were activated both by moving and by static emotional stimuli, indicating a general role in the interpretation of emotion. However, portions of the inferior frontal gyri and supplementary/pre-supplementary motor area showed task by motion interaction. These regions were most active during emotion judgements to static faces. Our results demonstrate a common neural substrate for recognizing static and moving facial expressions, but suggest a role for the inferior frontal gyrus in supporting simulation processes that are invoked more strongly to disambiguate static emotional cues.

Stop-signal response inhibition in schizophrenia : Behavioural, event-related potential and functional neuroimaging data

Inhibitory control deficits are well documented in schizophrenia, supported by impairment in an established measure of response inhibition, the stop-signal reaction time (SSRT). We investigated the neural basis of this impairment by comparing schizophrenia patients and controls matched for age, sex and education on behavioural, functional magnetic resonance imaging (fMRI) and event-related potential (ERP) indices of stop-signal task performance. Compared to controls, patients exhibited slower SSRT and reduced right inferior frontal gyrus (rIFG) activation, but rIFG activation correlated with SSRT in both groups. Go stimulus and stop-signal ERP components (N1/P3) were smaller in patients, but the peak latencies of stop-signal N1 and P3 were also delayed in patients, indicating impairment early in stop-signal processing. Additionally, response-locked lateralised readiness potentials indicated response preparation was prolonged in patients. An inability to engage rIFG may predicate slowed inhibition in patients, however multiple spatiotemporal irregularities in the networks underpinning stop-signal task performance may contribute to this deficit.

Cerebellar grey-matter deficits, cannabis use and first-episode schizophrenia in adolescents and young adults

Epidemiological data link adolescent cannabis use to psychosis and schizophrenia, but its contribution to schizophrenia neuropathology remains controversial. First-episode schizophrenia (FES) patients show regional cerebral grey- and white-matter changes as well as a distinct pattern of regional grey-matter loss in the vermis of the cerebellum. The cerebellum possesses a high density of cannabinoid type 1 receptors involved in the neuronal diversification of the developing brain. Cannabis abuse may interfere with this process during adolescent brain maturation leading to ‘schizophrenia-like’ cerebellar pathology. Magnetic resonance imaging and cortical pattern matching techniques were used to investigate cerebellar grey and white matter in FES patients with and without a history of cannabis use and non-psychiatric cannabis users. In the latter group we found lifetime dose-dependent regional reduction of grey matter in the right cerebellar lobules and a tendency for more profound grey-matter reduction in lobule III with younger age at onset of cannabis use. The overall regional grey-matter differences in cannabis users were within the normal variability of grey-matter distribution. By contrast, FES subjects had lower total cerebellar grey-matter : total cerebellar volume ratio and marked grey-matter loss in the vermis, pedunculi, flocculi and lobules compared to pair-wise matched healthy control subjects. This pattern and degree of grey-matter loss did not differ from age-matched FES subjects with comorbid cannabis use. Our findings indicate small dose-dependent effects of juvenile cannabis use on cerebellar neuropathology but no evidence of an additional effect of cannabis use on FES cerebellar grey-matter pathology.

Identification of pre-spike network in patients with mesial temporal lobe epilepsy

Background: Seizures and interictal spikes in mesial temporal lobe epilepsy (MTLE) affect a network of brain regions rather than a single epileptic focus. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have demonstrated a functional network in which hemodynamic changes are time-locked to spikes. However, whether this reflects the propagation of neuronal activity from a focus, or conversely the activation of a network linked to spike generation remains unknown. The functional connectivity (FC) changes prior to spikes may provide information about the connectivity changes that lead to the generation of spikes. We used EEG-fMRI to investigate FC changes immediately prior to the appearance of interictal spikes on EEG in patients with MTLE. Methods/principal findings: Fifteen patients with MTLE underwent continuous EEG-fMRI during rest. Spikes were identified on EEG and three 10 s epochs were defined relative to spike onset: spike (0–10 s), pre-spike (−10 to 0 s), and rest (−20 to −10 s, with no previous spikes in the preceding 45s). Significant spike-related activation in the hippocampus ipsilateral to the seizure focus was found compared to the pre-spike and rest epochs. The peak voxel within the hippocampus ipsilateral to the seizure focus was used as a seed region for FC analysis in the three conditions. A significant change in FC patterns was observed before the appearance of electrographic spikes. Specifically, there was significant loss of coherence between both hippocampi during the pre-spike period compared to spike and rest states. Conclusion/significance: In keeping with previous findings of abnormal inter-hemispheric hippocampal connectivity in MTLE, our findings specifically link reduced connectivity to the period immediately before spikes. This brief decoupling is consistent with a deficit in mutual (inter-hemispheric) hippocampal inhibition that may predispose to spike generation.