Fu-Shan Jaw

The loss of asymmetry and reduced interhemispheric connectivity in adolescents with autism: A study using diffusion spectrum imaging tractography

Evidence from neuroimaging and neurobiological studies suggests that abnormalities in cortical-cortical connectivity involving both local and long-distance scales may be related to autism. The present study analyzed the microstructural integrity of the long-range connectivity related to social cognition and language processing with diffusion tractography among adolescents with autism compared with neurotypical adolescents. Tract-specific analyses were used to study the long-range connectivity responsible for integrating social cognition and language processing. Specifically, three pairs of association fibers and three portions of callosal fiber tracts were analyzed. Generalized fractional anisotropy (GFA) values were measured along individual targeted fiber tracts to investigate alterations in microstructure integrity. The asymmetry patterns were also assessed in three pairs of association fibers. In neurotypical participants, we found a consistent leftward asymmetry in three pairs of association fibers. However, adolescents with autism did not demonstrate such asymmetry. Moreover, adolescents with autism had significantly lower mean GFA in three callosal fiber tracts than neurotypical participants. The loss of leftward asymmetry and reduction of interhemispheric connection in adolescents with autism suggest alterations of the long-range connectivity involved in social cognition and language processing. Our results warrant further investigation by combining developmental and neurocognitive data.

Microstructural white matter abnormalities in type 2 diabetes mellitus: A diffusion tensor imaging study

This study investigated whether diffusion tensor imaging (DTI) could identify potential abnormalities in type 2 diabetes mellitus (T2DM) patients without cognitive complaints compared to healthy controls. In addition, the existence of associations between diffusion measures and clinical parameters was examined. Forty T2DM patients and 97 non-diabetic controls completed a clinical and biochemistry examination. Structural MRI scans (DTI, T1, T2, FLAIR) were subsequently acquired with a 1.5 Tesla scanner. In addition to a global DTI analysis, voxel-based analysis was performed on the fractional anisotropy (FA), mean diffusivity (MD), and axial (AD) and transverse (TD) diffusivity maps to investigate regions that exhibit (i) WM differences between patients and controls; and (ii) associations between clinical measurements and these DTI indices. There were no significant differences in age, gender, and WM hyperintensity scores derived by the conventional MRI scans between controls and T2DM patients. For the T2DM patients, however, the MD of the brain parenchyma was significantly increased compared to controls and was positively correlated with disease duration. The voxel based analyses revealed (i) a significantly decreased FA in the bilateral frontal WM compared to controls which was mainly caused by an increased TD and not a decreased AD within these regions; (ii) a significant association between disease duration and microstructural properties in several brain regions including bilateral cerebellum, temporal lobe WM, right caudate, bilateral cingulate gyrus, pons, and parahippocampal gyrus. Our findings indicate that microstructural WM abnormalities and associations with clinical measurements can be detected with DTI in T2DM patients.

Imaging brain hemodynamic changes during rat forepaw electrical stimulation using functional photoacoustic microscopy

The present study reported the development of a novel functional photoacoustic microscopy (fPAM) system for investigating hemodynamic changes in rat cortical vessels associated with electrical forepaw stimulation. Imaging of blood optical absorption by fPAM at multiple appropriately-selected and distinct wavelengths can be used to probe changes in total hemoglobin concentration (HbT, i.e., cerebral blood volume [CBV]) and hemoglobin oxygen saturation (SO(2)). Changes in CBV were measured by images acquired at a wavelength of 570nm (lambda(570)), an isosbestic point of the molar extinction spectra of oxy- and deoxy-hemoglobin, whereas SO(2) changes were sensed by pixel-wise normalization of images acquired at lambda(560) or lambda(600) to those at lambda(570). We demonstrated the capacity of the fPAM system to image and quantify significant contralateral changes in both SO(2) and CBV driven by electrical forepaw stimulation. The fPAM system complements existing imaging techniques, with the potential to serve as a favorable tool for explicitly studying brain hemodynamics in animal models.

A New Scenario for Negative Functional Magnetic Resonance Imaging Signals: Endogenous Neurotransmission

Functional magnetic resonance imaging (fMRI) has revolutionized investigations of brain functions. Increases in fMRI signals are usually correlated with neuronal activation, but diverse explanations have been proposed for negative fMRI responses, including decreases in neuronal activity, the vascular-steal effect, and large increases in oxygen consumption. These possible scenarios, although encompassing a wide range of potential neurovascular responses, cannot yet be used to interpret certain types of negative fMRI signals. Recent studies have found that intravenous injection of dopamine D2 receptor (D2DR) agonist reduced the hemodynamic responses in the caudate–putamen (CPu); however, whether endogenous dopaminergic neurotransmission contributes to fMRI signals remains obscure. Since it has been suggested that the D2DR is involved in pain modulation, and the CPu shows equivocal fMRI signals during noxious stimulation, the present study established an animal model based on graded electrical stimulation to elicit different levels of nociception, and aimed to determine whether nociception-induced endogenous dopaminergic neurotransmission is sufficient to generate negative fMRI responses. Our results from cerebral blood volume (CBV)-weighted fMRI, Fos immunohistochemistry, and electrophysiological recording demonstrated a salient bilateral CBV decreases associated with heightened neuronal activity in the CPu induced by unilateral noxious electrical stimulation. In addition, preinjection of D2DR antagonist reduced the observed CBV decreases. Our findings reveal the role of the D2DR in regulating striatal vascular responses and suggest that endogenous neurotransmission-induced CBV decreases underlie negative fMRI signals. Hence, the influence of endogenous neurotransmission should be considered when interpreting fMRI data, especially in an area involved in strong vasoactive neurotransmission.

Ocular and cervical vestibular-evoked myogenic potentials: a study to determine whether air- or bone-conducted stimuli are optimal.

Objectives: The aim of this study was to determine whether bone-conducted vibration (BCV) or air-conducted sound (ACS) is the optimal mode for eliciting both ocular vestibular-evoked myogenic potentials (oVEMPs) and cervical VEMPs (cVEMPs). Design: Twelve healthy volunteers, five patients with unilateral chronic otitis media, and 10 patients with unilateral Meniere disease underwent oVEMP and cVEMP tests using ACS and BCV stimulation modes in a random order. Results: In healthy controls, BCV mode at Fz had a significantly higher response rate and larger nI-pI amplitude of oVEMPs than that of the ACS mode. In cVEMPs, a significantly higher response rate was noted in BCV mode at inion, when compared with ACS mode. However, no significant difference was noted in the p13-n23 amplitude between these two modes. In five chronic otitis media ears, absence of oVEMPs and cVEMPs in ACS mode and presence of oVEMPs and cVEMPs in BCV mode were shown. In 10 patients with Meniere disease, BCV mode elicited higher response rates of oVEMPs and cVEMPs in the pathological ears than ACS mode did. Conclusions: Using BCV mode, Fz and inion may be the optimal sites for eliciting oVEMPs and cVEMPs, respectively. Thus, BCV mode can be substituted for ACS mode to elicit oVEMPs and cVEMPs in the future, especially in “mass detection.” In contrast, ACS mode provides an essential clinical merit of site selectivity.

Whole-brain functional magnetic resonance imaging mapping of acute nociceptive responses induced by formalin in rats using atlas registration-based event-related analysis

Nociceptive neuronal activation in subcortical regions has not been well investigated in functional magnetic resonance imaging (fMRI) studies. The present report aimed to use the blood oxygenation level‐dependent (BOLD) fMRI technique to map nociceptive responses in both subcortical and cortical regions by employing a refined data processing method, the atlas registration‐based event‐related (ARBER) analysis technique. During fMRI acquisition, 5% formalin (50 μl) was injected into the left hindpaw to induce nociception. ARBER was then used to normalize the data among rats, and images were analyzed using automatic selection of the atlas‐based region of interest. It was found that formalin‐induced nociceptive processing increased BOLD signals in both cortical and subcortical regions. The cortical activation was distributed over the cingulate, motor, somatosensory, insular, and visual cortices, and the subcortical activation involved the caudate putamen, hippocampus, periaqueductal gray, superior colliculus, thalamus, and hypothalamus. With the aid of ARBER, the present study revealed a detailed activation pattern that possibly indicated the recruitment of various parts of the nociceptive system. The results also demonstrated the utilization of ARBER in establishing an fMRI‐based whole‐brain nociceptive map. The formalin induced nociceptive images may serve as a template of central nociceptive responses, which can facilitate the future use of fMRI in evaluation of new drugs and preclinical therapies for pain.

Ocular vestibular-evoked myogenic potentials elicited from monaural versus binaural acoustic stimulations

OBJECTIVE This study compared the ocular vestibular-evoked myogenic potentials (oVEMPs) that are elicited (recorded) in response to monaural and separately, simultaneous binaural acoustic stimulations. The optimal stimulation mode for oVEMPs was also determined. METHODS Twenty healthy volunteers (14 men and 6 women, aged from 22 to 33 years, mean 28 years) without any previous ear disorders were enrolled in this study. Each subject underwent oVEMP testing using monaural acoustic stimulation (Mon-oVEMP) with different stimulus intensities, and with bilateral recording. On another day, the same volunteers underwent oVEMP testing using simultaneous binaural acoustic stimulation and bilateral recording (Bin-oVEMP). RESULTS With 95 dB nHL tone burst stimulation, the biphasic nI-pI waveforms were recorded with maximal amplitudes from the electrodes located below the eyes contralateral to the side of acoustic stimulation while the subject was gazing upward. Significant correlations were identified between Mon-oVEMPs and Bin-oVEMPs with respect to threshold, latencies and amplitude. However, no significant difference existed between Mon-oVEMPs and Bin-oVEMPs in terms of the response rate, threshold, latency or amplitude. CONCLUSIONS The Bin-oVEMP test yields the same information as the Mon-oVEMP test, but the duration of recording in the former is shorter than the latter. SIGNIFICANCE The Bin-oVEMP test may be a more convenient screening tool for evaluating the crossed vestibulo-ocular reflex.

Detection of the third and fourth heart sounds using Hilbert-Huang transform

BackgroundThe third and fourth heart sound (S3 and S4) are two abnormal heart sound components which are proved to be indicators of heart failure during diastolic period. The combination of using diastolic heart sounds with the standard ECG as a measurement of ventricular dysfunction may improve the noninvasive diagnosis and early detection of myocardial ischemia.MethodsIn this paper, an adaptive method based on time-frequency analysis is proposed to detect the presence of S3 and S4. Heart sound signals during diastolic periods were analyzed with Hilbert-Huang Transform (HHT). A discrete plot of maximal instantaneous frequency and its amplitude was generated and clustered. S3 and S4 were recognized by the clustered points, and performance of the method was further enhanced by period definition and iteration tracking.ResultsUsing the proposed method, S3 and S4 could be detected adaptively in a same method. 90.3% of heart sound cycles with S3 were detected using our method, 9.6% were missed, and 9.6% were false positive. 94% of S4 were detected using our method, 5.5% were missed, and 16% were false positive.ConclusionsThe proposed method is adaptive for detecting low-amplitude and low-frequency S3 and S4 simultaneously compared with previous detection methods, which would be practical in primary care.

Increased risk of stroke in the year after a hip fracture: a population-based follow-up study.

Background and Purpose— Stroke is a documented risk factor for hip fracture. However, no documented studies are available on the risk of stroke among patients with hip fracture. This study investigated the frequency and risk of stroke after hip fracture using a nationwide population-based study. Methods— The study cohort included 2101 patients hospitalized with a principal diagnosis of hip fracture from 2001 to 2004. The comparison cohort consisted of 6303 randomly selected subjects matched on sex, age, and year of index healthcare use as controls. We tracked patients for a 1-year period from their index healthcare encounter to identify those who had a stroke. Stratified Cox proportional hazard regression was performed to evaluate the association of hip fracture with subsequent stroke during 1-year follow-up. Results— Of a total of 8404 patients, 86 (4.1%) from the study group and 170 (2.7%) from the comparison group had strokes during the follow-up period (P<0.001). The stratified Cox proportional analysis shows that the 1-year crude hazard of stroke among patients with hip fracture was 1.55 times (95% CI, 1.19 to 2.03; P=0.001) that of the comparison group. Furthermore, after adjusting for the major cardiovascular risk factors, the increased stroke risk of patients with hip fracture persisted at about the same level as in the unadjusted analysis (hazard ratio, 1.53; 95% CI, 1.17 to 2.01; P=0.002). Conclusion— Hip fracture is associated with increased risk of stroke in the next year.

Auditory event-related potential of subjects with suspected pre-psychotic state and first‐episode psychosis

BACKGROUND Recent schizophrenia research exploring the complicated pathogenesis of schizophrenia has focused on the subjects with at-risk mental states in order to exclude the influence of confounding factors. This study explores 3 sets of auditory-related event potentials in subjects with different risk levels of psychosis. METHODS Subjects were recruited from the SOPRES study in Taiwan. P50 and N100 using an auditory paired-click paradigm and duration MMN were assessed on 32 first-episode psychosis (FEP), 30 ultra-high risk (UHR), 37 E-BARS (early/broad at-risk mental states) participants and 56 controls. RESULTS MMN was correlated with neither P50 nor N100, whereas many parameters of the latter two were intercorrelated with each other. Compared to healthy controls, MMNs were significantly lower in all 3 clinical groups (E-BARS, UHR and FEP). A gradient of sensory-gating deficits, manifested by increased P50 ratios (S2/S1) and decreased N100 differences, across different levels of clinical severity was suggested by a linear trend. For the UHR subjects, P50 gating ratio, N100 gating ratio, N100 difference, and N100S2 amplitude might be potential indicators to discriminate converters from non-converters. CONCLUSIONS By including subjects with E-BARS, our results provide new insight regarding pre-attentive auditory event-related potential in subjects across different risk levels of psychotic disorders. Impaired deviance detection shown by MMNs already exists in people at a pre-psychotic state regardless of clinical severity, while sensory-gating deficits shown by P50/N100 varies depending on the risk levels in prodromal period. Further longitudinal research exploring the relationship between ERPs and subjects with a suspected pre-psychotic state is needed.