The Posterior Limb of the Internal Capsule as the Subcortical Transitional Zone of the Anterior and Posterior Circulations: Insights from Human 7T MRI.

BACKGROUND: In patients with cerebral infarction, identifying the distribution of infarction and the relevant artery is essential for ascertaining the underlying vascular pathophysiological mechanisms and preventing subsequent stroke. However, visualization of the basal perforating arteries (BPAs) has had limited success, and simultaneous viewing of background anatomical structures has only rarely been attempted in living human brains. Our study aimed at identifying the BPAs with 7T MRI and evaluating their distribution in the subcortical structures, thereby showing the clinical significance of the technique. METHODS: Twenty healthy subjects and 1 patient with cerebral infarction involving the posterior limb of the internal capsule (ICpost) and thalamus underwent 3-dimensional fast spoiled gradient-echo sequence as time-of-flight magnetic resonance angiography (MRA) at 7T with a submillimeter resolution. The MRA was modified to detect inflow signals from BPAs, while preserving the background anatomical signals. BPA stems and branches in the subcortical structures and their origins were identified on images, using partial maximum intensity projection in 3 dimensions. RESULTS: A branch of the left posterior cerebral artery (PCA) in the patient ran through both the infarcted thalamus and ICpost and was clearly the relevant artery. In 40 intact hemispheres in healthy subjects, 571 stems and 1,421 branches of BPAs were detected in the subcortical structures. No significant differences in the numbers of stems and branches were observed between the intact hemispheres. The numbers deviated even less across subjects. The distribution analysis showed that the subcortical structures of the telencephalon, such as the caudate nucleus, anterior limb of the internal capsule, and lenticular nucleus, were predominantly supplied by BPAs from the anterior circulation. In contrast, the thalamus, belonging to the diencephalon, was mostly fed by BPAs from the posterior circulation. However, compared with other subcortical structures, the ICpost, which marks the anatomical boundary between the telencephalon and the diencephalon, was supplied by BPAs with significantly more diverse origins. These BPAs originated from the internal carotid artery (23.1%), middle cerebral artery (38.5%), PCA (17.3%), and the posterior communicating artery (21.1%). CONCLUSIONS: The modified MRI method allowed the detection of the relevant BPA within the infarcted area in the stroke survivor as well as the BPAs in the subcortical structures of living human brains. Based on in vivo BPA distribution analyses, the ICpost is the transitional zone of the anterior and posterior cerebral circulations.

Noninvasive scalp recording of cortical auditory evoked potentials in the alert macaque monkey.

Scalp-recorded evoked potentials (EP) provide researchers and clinicians with irreplaceable means for recording stimulus-related neural activities in the human brain, due to its high temporal resolution, handiness, and, perhaps more importantly, non-invasiveness. This work recorded the scalp cortical auditory EP (CAEP) in unanesthetized monkeys by using methods that are essentially identical to those applied to humans. Young adult rhesus monkeys (Macaca mulatta, 5-7 years old) were seated in a monkey chair, and their head movements were partially restricted by polystyrene blocks and tension poles placed around their head. Individual electrodes were fixated on their scalp using collodion according to the 10-20 system. Pure tone stimuli were presented while electroencephalograms were recorded from up to nineteen channels, including an electrooculogram channel. In all monkeys (n = 3), the recorded CAEP comprised a series of positive and negative deflections, labeled here as macaque P1 (mP1), macaque N1 (mN1), macaque P2 (mP2), and macaque N2 (mN2), and these transient responses to sound onset were followed by a sustained potential that continued for the duration of the sound, labeled the macaque sustained potential (mSP). mP1, mN2 and mSP were the prominent responses, and they had maximal amplitudes over frontal/central midline electrode sites, consistent with generators in auditory cortices. The study represents the first noninvasive scalp recording of CAEP in alert rhesus monkeys, to our knowledge.

Neural mechanisms underlying the orienting response to subject's own name: an event-related potential study.

Neural processes underlying the orienting response (OR) to subject's own name (SON) were investigated using the oddball paradigm. Subjects were presented with SON, subject's parent's name, and unfamiliar persons' names while they played a video game and ignored the auditory stimuli. A P3a-like frontal positivity (P440, 440 ms) indexing OR was elicited by SON only when it was the rare stimulus and its amplitude decreased with the repeated presentation of SON. Preceding the P440, SON consistently elicited an early frontal negativity (SON negativity, 170-270 ms), including when SON was the high-probability stimulus, and unlike the P440, this negativity did not habituate. These results conform to the hypothesis that early preattentive processing of speech sounds distinguishes SON from other names irrespective of short-term stimulus context, and that this culminates in an OR only when SON is evaluated as being contextually meaningful.

Functional asymmetry in primary auditory cortex for processing musical sounds: temporal pattern analysis of fMRI time series.

Hemispheric differences in the temporal processing of musical sounds within the primary auditory cortex were investigated using functional magnetic resonance imaging (fMRI) time series analysis on a 3.0 T system in right-handed individuals who had no formal training in music. The two hemispheres exhibited a clear-cut asymmetry in the time pattern of fMRI signals. A large transient signal component was observed in the left primary auditory cortex immediately after the onset of musical sounds, while only sustained activation, without an initial transient component, was seen in the right primary auditory cortex. The observed difference was believed to reflect differential segmentation in primary auditory cortical sound processing. Although the left primary auditory cortex processed the entire 30-s musical sound stimulus as a single event, the right primary auditory cortex had low-level processing of sounds with multiple segmentations of shorter time scales. The study indicated that musical sounds are processed as 'sounds with contents', similar to how language is processed in the left primary auditory cortex.

Central auditory processing of noncontextual consonance in music: an evoked potential study.

The consonance of individual chords presented out of musical context, or the noncontextual consonance of chords, is usually defined as the absence of roughness, which is a sensation perceived when slightly mistuned frequencies are not clearly resolved in the cochlea. The present work uses evoked potentials to demonstrate that the absence of roughness is not sufficient to explain the entirety of noncontextual consonance perception. Presented with a random sequence of various pure-tone intervals (0-13 semitones), listeners' cerebral cortical activities distinguished these stimuli according to their noncontextual consonance in a manner consistent with standard musical practice, even when the intervals exceeded the critical bandwidth (approximately three semitones). The roughness-based model of noncontextual consonance could not account for this result because these wide intervals had indistinguishably low levels of roughness. Further, this effect was evident only in musicians, indicating plasticity in the underlying neural mechanisms. The results are consistent with the hypothesis that, although the absence of roughness may represent an important aspect of noncontextual consonance, properties of intervals other than those related to roughness also contribute to this perception, underpinned by neural activity in the central auditory system that can be plastically modified by experience.

Inhibition of aquaporin 4 by antiepileptic drugs.

The potential of antiepileptic drugs (AEDs) to inhibit the water transport properties of aquaporin 4 (AQP4) was investigated using a combination of in silico and in vitro screening methods. Virtual docking studies on 14 AEDs indicated a range of docking energies that spanned approximately 40 kcal/mol, where the most stabilized energies were consistent with that of the previously identified AQP4 inhibitor acetazolamide. Nine AEDs and one bio-active metabolite were further investigated in a functional assay using AQP4 expressing Xenopus oocytes. Seven of the assayed compounds were found to inhibit AQP4 function, while three did not. A linear correlation was indicated between the in silico docking energies and the in vitro AQP4 inhibitory activity at 20 microM.

Brain developmental abnormalities in Prader-Willi syndrome detected by diffusion tensor imaging.

OBJECTIVE: The purpose of this work was to detect brain developmental abnormalities in Prader-Willi syndrome by using diffusion tensor imaging based on a high-field MRI system. METHODS: Eight patients with Prader-Willi syndrome and 8 age- and gender-matched normal control subjects were examined using a high-field (3.0 T) MRI system. Trace value and fractional anisotropy were assessed simultaneously in multiple representative brain regions: the deep gray matter (putamen, caudate head, and dorsomedial thalamus) and the white matter structures (frontal and parietal white matter, posterior limb of internal capsule, and corpus callosum). RESULTS: In Prader-Willi syndrome patients, trace value was found to be significantly higher in the left frontal white matter and the left dorsomedial thalamus, whereas fractional anisotropy was significantly reduced in the posterior limb of the internal capsule bilaterally, the right frontal white matter, and the splenium of the corpus callosum. The observed diffusivity characteristics indicate developmental abnormalities in these areas, which are highly consistent with the clinical features of Prader-Willi syndrome. CONCLUSIONS: The study provides the first objective evidence that Prader-Willi syndrome patients indeed have developmental abnormalities in specific areas of the brain, providing a new window toward understanding the pathophysiology of Prader-Willi syndrome.

Electrophysiological correlates of absolute pitch and relative pitch.

The temporal and spatial characteristics of the cortical processes responsible for absolute pitch (AP) and relative pitch (RP) were investigated by multi-channel event-related potentials (ERPs). Compared to listening, pitch-naming of tones in non-possessors of AP elicited three ERP components (P3b, parietal positive slow wave, frontal negative slow wave) over parietal and frontal scalp between 300 and 900 ms in latency, representing the cortical processes for RP. Possessors of AP elicited a unique left posterior-temporal negativity ('AP negativity') at 150 ms in both listening and pitch-naming conditions, representing the cortical processes for AP that were triggered by pitch input irrespective of the task the subjects were asked to perform. Congruency of auditory Stroop stimuli modulated the amplitudes of parietal positive slow wave (non-possessors of AP) and 'AP negativity' (possessors of AP), confirming that these components reflect the verbal labeling or pitch-to-pitch-name associative transformation that is central to pitch-naming. These results are consistent with the hypothesis that AP is subserved by neuronal processes in the left auditory association cortex that occur earlier and more automatically than the processes for RP, which involve broader areas of the cortex over longer periods of time.

Cortical processing of musical consonance: an evoked potential study.

Cortical processes underlying perception of musical consonance were investigated by long-latency auditory evoked potentials (EPs). Subjects listened to a random sequence of dyadic pure tones paired at various pitch intervals (1, 4, 6, 7, or 9 semitones). Amplitudes of P2 and N2 components of auditory EPs were significantly modulated by pitch interval of the dyads, being most negative for 1 semitone (minor second) and least negative or most positive for 7 semitones (perfect fifth). The results indicate that neural processing of consonance depend not only on peripheral mechanisms in the inner ear but also on higher associative processing of pitch relationships in the cerebral cortex.

Molecular cloning and characteristics of a novel zinc finger protein and its splice variant whose transcripts are expressed during spermatogenesis.

Testicular zinc finger protein (TZF) has a zinc finger motif of the Cys2-His2 type and its transcript is expressed predominantly in mouse spermatogenic cells. Using the fragment of TZF as a probe, we isolated the alternative splice variant form (TZF-L) from mouse testis cDNA library. Analysis of the open reading frame of each cDNA indicated that TZF and TZF-L were polypeptides of 942 and 2025 amino acid residues, respectively, and the N-terminal 902 amino acids of TZF-L were identical to those of TZF. The C-terminal region of TZF-L had more a zinc finger motif of the Cys2-His2 type and poly-Glu and poly-Pro regions. The mouse TZF/TZF-L gene spanned >20 kb and consisted of 11 exons. RT-PCR analysis of the expression level of mRNAs for mouse TZF and TZF-L showed that both transcripts are highly expressed in testis and moderately in kidney and ovary. Elevated expression of both transcripts during testicular development in mice was restricted to spermatocytes at the pachytene stage of meiotic prophase. Fusion proteins with GFP also demonstrated the nuclear localization of TZF and TZF-L. These experiments suggest that TZF and TZF-L may act to control the gene activity during spermatogenesis.

Effect of ninjin-youei-to on Th1/Th2 type cytokine production in different mouse strains.

Ninjin-youei-to (NYT; ren-shen-yang-rong-tang in Chinese) is a traditional herbal formula, which is widely used in Japan, Korea and China to modulate physiological immunity. The effects of oral administration of NYT on cytokine production from splenocytes were investigated in both C57BL/6 and BALB/c mice in which Th1 and Th2 were dominant, respectively. Splenocytes from C57BL/6 and BALB/c mice, which took NYT orally forfour weeks, were cultured with anti-mouse CD3 mAb, and the supernatant was examined for cytokine production using enzyme-linked immunosorbent assay (ELISA). Administration of NYT to C57BL/6 mice, increased the production of interleukin-4 (IL-4) significantly, and slightly decreased interferon-y (IFN-gamma) production from splenocytes. In contrast, the same treatment significantly increased IFN-gamma secretion from splenocytes of BALB/c mice. No remarkable changes of IL-12 production from splenocytes were observed in either strain of mice. These results suggest that oral administration of NYT ameliorates the excessive inclination of Th1 and Th2 type cytokine production, and NYT may provide a beneficial effects for the treatment of diseases caused by a skewed Th1-Th2 balance in the immune system.

Effect of orally administered Hochu-ekki-to, a Japanese herbal medicine, on contact hypersensitivity caused by repeated application of antigen.

The effects of oral administration of Hochu-ekki-to (HET; bu-zhong-yi-qi-tang in Chinese), a traditional Japanese and Chinese herbal medicine, on chronic contact hypersensitivity were investigated. HET suppressed ear swelling due to chronic contact hypersensitivity caused by repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB). HET significantly suppressed not only increases in hapten-specific immunoglobulin E (IgE) and IgG1 titer due to repeated application of TNCB, but also total IgE and IgG1 concentration in the serum. Interleukin 4 (IL-4) level in inflamed ear tissue was significantly increased by repeated application of TNCB, and this increase in IL-4 level in the ear was significantly suppressed by oral administration of HET. Interferon gamma (IFN-gamma), IL-2, IL-5, IL-10 and IL-12 levels are not changed as much as IL4 by TNCB and HET did not alter these cytokines as much as IL-4. These results suggest that oral administration of HET suppresses chronic contact hypersensitivity, and it can be assumed that the suppression of serum Ig E and Ig G1 and IL-4 in inflamed ear.

Effect of mild hypothermia on energy state recovery following transient forebrain ischemia in the gerbil.

A transient (lasting for 15 min) bilateral carotid artery occlusion model was created by using male Mongolian gerbils ( n=20, weight 50-60 g). The animals were divided into a group with mild hypothermia (34 degrees C, n=10) and a normothermic group (37 degrees C, n=10). High-energy phosphate metabolism (ATP, PCr, Pi) and intracellular pH were sequentially measured using (31)P-MRS during ischemia and after reperfusion for 1 week. The same animals were also subjected to a histopathological evaluation. During ischemia, there were no statistically significant differences between the two groups in the quantities of the metabolites. However, after reperfusion the rate of metabolic recovery by the mildly hypothermic (MH) group was significantly higher (by 10-20%) than the normothermic (NT) group. The intracellular pH decreased about 0.4 in both groups after ischemia; and after reperfusion the intracellular pH of the MH group returned to baseline levels faster than in the NT group. One week after ischemia, energy metabolism gradually decreased about 10-20% in both groups. In the histopathological evaluation, pyramidal cell damage in the hippocampus was 33% on average in the MH group and 79% in the NT group. The neuronal damage to the cerebral cortex was 26% in the MH group and 61% in the NT group. Astrocyte reactivity in the hippocampus and cerebral cortex was 2.9% and 1.1% in the MH group and 9.7% and 5.2% in the NT group. The results of this experiment indicate that the protective effect of mild hypothermia is due to the high recovery rate of ATP and PCr and the prevention of a secondary decline in high phosphate energy.