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Encoding activity in the medial temporal lobe examined with anatomically constrained fMRI analysis.

Functional neuroimaging studies have produced a sizable number of observations of increased activity in the human medial temporal lobe (MTL) during encoding of novel memories. The studies have suggested possible functional specialization within the anatomical components of the MTL (hippocampus and the entorhinal, perirhinal, and parahippocampal cortical areas). Neuroimaging studies have just begun to link anatomical regions to specific functions. To address functional specialization hypothesis, a method is described for using high-resolution structural information from magnetic resonance imaging MRI to constrain the analysis of functional magnetic resonance imaging (fMRI) data, for independent assessment of functional activity change in each component of the MTL. With this method, increased activity was detected throughout the MTL in a group of participants (n = 5) who encoded novel pictures. A separate group (n = 5) who encoded words exhibited lower-levels of evoked activity. Laterality effects were found reflecting increased right hemisphere activity during picture encoding (parahippocampal cortex) and increased left hemisphere activity during word encoding (posterior hippocampus and parahippocampal cortex). Neither condition provided evidence for greater activity in the posterior hippocampus than in the anterior hippocampus during encoding, although the greatest increases in activity were observed in the parahippocampal cortex. The anatomically driven methodology is shown to provide detailed comparison of levels of activity change across specific brain areas and to provide increased sensitivity to functional change in each region of the MTL.

Adult↗

Encoding versus retrieval of spatial memory: double dissociation between the dentate gyrus and the perforant path inputs into CA3 in the dorsal hippocampus.

The hippocampus is an essential neural structure for spatial memory. Computational models suggest that the CA3 subregion of the hippocampus plays an essential role in encoding and retrieval of spatial memory. The perforant path (PPCA3) and dentate gyrus (DG)-mediated mossy fibers (MFs) compose major afferent inputs into CA3. A possible functional dissociation between these afferent inputs was attempted using a simple navigation test (i.e., the modified Hebb-Williams maze). Behavioral testing was combined with electrolytic lesions of PPCA3 or neurotoxic lesions of the DG, to eliminate each afferent input into CA3. Lesions in either afferent input into CA3 affected learning of an effective navigational path on the maze. The contributions of the two CA3 afferent inputs, however, were different regarding encoding and retrieval of memory measured based on indices operationally defined for the behavioral paradigm (i.e., encoding, the number of errors reduced within a day; retrieval, the number of errors reduced between days). The DG-lesioned animals exhibited deficits regarding the encoding index, but not the retrieval index, whereas the PPCA3-lesioned rats displayed deficits regarding the retrieval index, but not the encoding index. The results suggest that the two major afferent inputs of CA3 may contribute differentially to encoding and retrieval of spatial memory.

Animals↗

EGF homologous sequences encoded in the genome of Drosophila melanogaster, and their relation to neurogenic genes.

The function of the neurogenic genes of Drosophila melanogaster is required for a normal pattern of commitment of neural and epidermal progenitor cells. In the course of searching for a molecular basis for the functional interrelationships that exist between the neurogenic genes, fragments of cloned DNA from the genes master mind (mam), Delta (Dl), Enhancer of split [E(spl)] and Notch (N) were hybridized to each other. Strong cross-hybridization was observed between a fragment of the Dl gene and a fragment of the N gene encoding a peptide with homology to several proteins of mammals, including the epidermal growth factor (EGF). Sequencing of this Dl fragment revealed an open reading frame encoding four EGF-like repeats with homology to the repeats found in the N gene. Screening genomic and cDNA libraries under conditions of reduced stringency with Dl and N probes that encode EGF-like repeats uncovered several cross-hybridizing clones, suggesting that other Drosophila genes may also encode such peptides. Part of a cross-hybridizing cDNA clone, derived from a gene located at position 95F on the third chromosome, was sequenced and found to encode five repeats with homology to those encoded by N and Dl. Preliminary evidence on the spatial pattern of transcription indicates that the gene at position 95F is regulated in its expression, as it is transcribed in all ectodermal derivatives, with the exception of the central nervous system. Indirect evidence suggests that this clone may derive from the crumbs (crb) gene, which is likely to be an hitherto unknown neurogenic gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Multilevel wavelet-transform encoding in MRI.

This paper explores an alternative to standard Fourier MRI called wavelet-transform encoding. Spatially selective radiofrequency (RF) pulses are used to excite slice profiles in the shape of the wavelet-basis functions of a discrete wavelet transform. Our implementation on a standard commercial whole body MRI system resolves one spatial dimension through wavelet encoding and orthogonal directions through conventional frequency encoding and rectangular-slice selection. The wavelet transform is described as a method for multiresolution analysis, and we show how a high resolution MR image can be constructed from lower resolution images, representing the approximation and detail structures of the object. A multiple level architecture of the wavelet reconstruction is described, thereby allowing wavelet-encoded images to be reconstructed through several modes. Multilevel wavelet-encoded images of a gel phantom are presented that show comparable image quality to Fourier-encoded images of similar signal-to-noise ratio. However, a chemical-shift artifact is identified with this particular implementation.

Artifacts↗

Fourier imaging using rf phase encoding.

Fourier imaging methods encode information in the amplitudes and phases of a NMR signal over multiple acquisitions. Several of the techniques that can be used for encoding this information are reviewed and a general theory of phase encoding presented. The discussion is then extended to include encoding as part of the rf excitation sequence. Radiofrequency phase encoding can be obtained using tailored excitation techniques or special-purpose rf field gradient coils, and may be applied prior to excitation or incorporated within the excitation or refocusing pulses. This phase-encoding method may be used for spatial and spectral discrimination, as well as being combined with other methods of image formation. An example of the proposed imaging method is described which enables Fourier imaging of short T2 signals.

Fourier Analysis↗

Wavelet-encoded MR imaging.

Wavelet encoding is presented and compared to phase encoding. In wavelet encoding a distribution of spins is excited by a slice selective RF pulse; for each repetition time the distribution excited has the profile of a wavelet at different scale and translation. The spin density can be reconstructed with an inverse wavelet transform. Wavelet encoding has three advantages over phase encoding: (1) there is no Gibb's ringing from partial volume effects, (2) the effective repetition time can be 36 times the repetition time for a 256 x 256 image, and (3) motion artifacts are local and dramatically reduced. Using wavelet encoding, a 256 x 256 T2-weighted projection image can be acquired in 33 s.

Artifacts↗

Blood flow measurement using variable velocity encoding in the RR interval.

Velocity-encoded phase imaging using asynchronous gating requires input of a velocity encoding value to set the velocity sensitivity of the pulse sequence. The raw data interpolation and reconstruction scheme that the pulse sequence uses forces the encoding value to be constant throughout the RR interval. The sequence and the raw data interpolation scheme were modified to allow two velocity encodings during the RR interval. Two-hundred cm/s encoding was used in systole, and 30 cm/s in diastole. Changing the encoding in diastole significantly improved the accuracy and precision of ascending aorta flow measurements.

Aorta↗

Wavelet encoding for 3D gradient-echo MR imaging.

An implementation of wavelet encoding to resolve one spatial direction of a three-dimensional gradient-echo magnetic resonance image is described. This is the first report of the use of wavelet encoding with a relatively short repetition time for rapid image acquisition. An important feature of this implementation is that it allows wavelet-encoded images to be reconstructed without phase correction. The images show no discernible degradation compared with images acquired with phase encoding or scaling-function encoding instead of wavelet encoding. In addition to describing the implementation, typical sources of phase errors are investigated both theoretically and experimentally.

Magnetic Resonance Imaging↗

Displacement-encoded cardiac MRI using cosine and sine modulation to eliminate (CANSEL) artifact-generating echoes.

Displacement-encoded imaging with stimulated echoes (DENSE) and harmonic phase imaging (HARP) employ 1-1 spatial modulation of magnetization to cosine modulate the longitudinal magnetization as a function of position at end diastole. Later in the cardiac cycle they sample the cosine-modulated signal and compute myocardial strain from the signal phase. The sampled signal generally includes three distinct echoes: 1) a displacement-encoded stimulated echo, 2) the complex conjugate of the displacement-encoded echo, and 3) an echo arising from T1 relaxation. If the T1-relaxation and complex conjugate echoes are suppressed, then a phase image representing just the displacement-encoded echo can be reconstructed. In the present study, the use of cosine and sine modulation to eliminate (CANSEL) the T1-relaxation and complex conjugate echoes was investigated. With the use of CANSEL, it was demonstrated that DENSE accurately measures through-plane as well as in-plane components of tissue motion. Also, DENSE with CANSEL artifact suppression can provide increased signal-to-noise ratio (SNR) secondary to reduced intravoxel dephasing by using relatively low displacement-encoding frequencies. For applications that employ DENSE imaging with multiple acquisitions, the CANSEL technique can suppress artifact-generating echoes without placing constraints on the displacement-encoding frequency and direction.

Animals↗

Adenoviral vector cytotoxicity depends in part on the transgene encoded.

First-generation adenoviral vectors induce G(2)/M arrest and cell death at high multiplicities of infection (m.o.i.'s) in vitro. It is unclear whether this cytotoxicity is entirely adenoviral gene related or influenced in part by the encoded transgene. We examined this question in epithelial cells using seven vectors at relatively low (50) or higher (200) m.o.i.'s. The vectors contained no transgene (+/-promoter), transgenes encoding a cytoplasmic reporter protein (two luciferase constructs; beta-galactosidase), or transgenes encoding a secretory protein (alpha1-antitrypsin; growth hormone). After 24 h with a m.o.i. of 50, vectors encoding cytoplasmic reporter proteins led to greatest cytotoxicity (approximately 35-40% cells in G(2)/M). Vectors without a transgene resulted in lower cytotoxicity (approximately 15%, minus, or 23%, plus promoter, cells in G(2)/M). Vectors encoding secretory proteins led to approximately 22-25% cells in G(2)/M. A similar pattern resulted when cell number was measured. Results were unrelated to the steady-state levels of transgene product. At the higher m.o.i., all vectors caused substantial growth retardation. This is the first demonstration that adenoviral vector-induced cytotoxic effects are in part related to the transgene encoded.

Adenoviridae↗

Mapping of four mouse genes encoding eye lens-specific structural, gap junction, and integral membrane proteins: Cryba1 (crystallin beta A3/A1), Crybb2 (crystallin beta B2), Gja8 (MP70), and Lim2 (MP19).

Four genes encoding eye lens-specific proteins, potential candidate genes for congenital cataract (CC) mutations, were mapped in the mouse genome using a panel of somatic cell hybrids and DNAs from the EU-CIB (European Collaborative Interspecific Backcross). Two of them are lens fiber cell structural proteins: the Cryba1 locus encoding crystallinbetaA3/A1 maps to chromosome 11, 2.5 +/- 2.5 cM distal to D11Mit31, and the Crybb2 locus encoding crystallinbetaB2 maps to chromosome 5, 9.1 +/- 4.3 cM distal to D5Mit88. The other two genes encode lens-specific gap junction and integral membrane proteins, respectively: The Gja8 locus encoding gap juction membrane channel protein alpha8, also called connexin50 or MP70, maps to chromosome 3, 11.9 +/- 5.0 cM distal to D3Mit22, and the Lim2 locus encoding lens intrinsic membrane protein 2, also called MP19, maps to chromosome 7, 2.5 +/- 2.5 cM proximal to Ngfg. All four map positions, when compared with the corresponding positions in human, lie within known regions of conserved synteny between mouse and human chromosomes.

Animals↗

Testis-specific expression of a functional retroposon encoding glucose-6-phosphate dehydrogenase in the mouse.

The X-chromosomal gene glucose-6-phosphate dehydrogenase (G6pd) is known to be expressed in most cell types of mammalian species. In the mouse, we have detected a novel gene, designated G6pd-2, encoding a G6PD isoenzyme. G6pd-2 does not contain introns and appears to represent a retroposed gene. This gene is uniquely transcribed in postmeiotic spermatogenic cells in which the X-encoded G6pd gene is not transcribed. Expression of the G6pd-2 sequence in a bacterial system showed that the encoded product is an active enzyme. Zymogramic analysis demonstrated that recombinant G6PD-2, but not recombinant G6PD-1 (the X-chromosome-encoded G6PD), formed tetramers under reducing conditions. Under the same conditions, G6PD tetramers were also found in extracts of spermatids and spermatozoa, indicating the presence of G6pd-2-encoded isoenzyme in these cell types. G6pd-2 is one of the very few known expressed retroposons encoding a functional protein, and the presence of this gene is probably related to X chromosome inactivation during spermatogenesis.

Amino Acid Sequence↗

Human hydroxysteroid sulfotransferase SULT2B1: two enzymes encoded by a single chromosome 19 gene.

We have cloned and characterized cDNAs that encode two human hydroxysteroid sulfotransferase (SULT) enzymes, SULT2B1a and SULT2B1b, as well as the single gene that encodes both of these enzymes. The two cDNAs differed at their 5'-termini and had 1050- and 1095-bp open reading frames that encoded 350 and 365 amino acids, respectively. The amino acid sequences encoded by these cDNAs included "signature sequences" that are conserved in all known cytosolic SULTs. Both cDNAs appeared, on the basis of amino acid sequence analysis, to be members of the hydroxysteroid SULT "family, " SULT2, but they were only 48% identical in amino acid sequence with the single known member of that family in humans, SULT2A1 (also referred to as DHEA ST). Northern blot analysis demonstrated the presence of SULT2B1 mRNA species approximately 1.4 kb in length in human placenta, prostate, and trachea and-faintly-in small intestine and lung. Expression of the two human SULT2B1 cDNAs in COS-1 cells showed that both of the encoded proteins catalyzed sulfation of the prototypic hydroxysteroid SULT substrate, dehydroepiandrosterone, but both failed to catalyze the sulfate conjugation of 4-nitrophenol or 17beta-estradiol, prototypic substrates for the phenol and estrogen SULT subfamilies. Both of these cDNAs were encoded by a single gene, SULT2B1. The locations of most exon-intron splice junctions in SULT2B1 were identical to those of the only other known human hydroxysteroid SULT gene SULT2A1 (previously STD). The divergence in 5'-terminal sequences of the two SULT2B1 cDNAs resulted from alternative transcription initiation prior to different 5' exons, combined with alternative splicing. SULT2B1 mapped to human chromosome band 19q13.3, approximately 500 kb telomeric to the location of SULT2A1.

Alternative Splicing↗

Organization of the mouse cardiac natriuretic peptide locus encoding BNP and ANP.

The genes encoding the mouse atrial natriuretic peptide and B-type natriuretic peptide were previously shown to be physically linked on mouse chromosome 4 (Steinhelper ME, 1993, Structure, expression, and genomic mapping of the mouse natriuretic peptide type-B gene. Circ Res 72: 984-992). In the present study the spatial relationship and orientation of the mouse atrial natriuretic peptide and B-type natriuretic peptide transcription units were identified and a physical map of the mouse cardiac natriuretic peptide locus was obtained. To this end, genomic clones encoding atrial natriuretic peptide and B-type natriuretic peptide were isolated from a mouse genomic library in bacteriophage P1. Three independent clones encoding atrial natriuretic peptide were isolated and two of these also encode B-type natriuretic peptide. Both transcripts were shown to arise from the same DNA strand, with B-type natriuretic peptide encoded approximately 15 kb 5'-of atrial natriuretic peptide based on field inversion gel electrophoresis of fragments amplified with specific oligonucleotides. This finding was confirmed by isolation of subclones comprising the entire locus and by blot hybridization analysis of mouse genomic DNA. The results show that the genes encoding the two natriuretic peptides expressed predominantly in mammalian cardiac myocytes are organized in tandem on mouse chromosome 4. This information provides a physical framework for investigating mechanisms that regulate transcription of the cardiac natriuretic peptide locus.

Animals↗

Effective auditory-verbal encoding activates the left prefrontal and the medial temporal lobes: A generalization to illiterate subjects.

Recent event-related FMRI studies indicate that the prefrontal (PFC) and the medial temporal lobe (MTL) regions are more active during effective encoding than during ineffective encoding. The within-subject design and the use of well-educated young college students in these studies makes it important to replicate these results in other study populations. In this PET study, we used an auditory word-pair association cued-recall paradigm and investigated a group of healthy upper middle-aged/older illiterate women. We observed a positive correlation between cued-recall success and the regional cerebral blood flow of the left inferior PFC (BA 47) and the MTLs. Specifically, we used the cued-recall success as a covariate in a general linear model and the results confirmed that the left inferior PFC and the MTL are more active during effective encoding than during ineffective encoding. These effects were observed during encoding of both semantically and phonologically related word pairs, indicating that these effects are robust in the studied population, that is, reproducible within group. These results generalize the results of Brewer et al. (1998, Science 281, 1185-1187) and Wagner et al. (1998, Science 281, 1188-1191) to an upper middle aged/older illiterate population. In addition, the present study indicates that effective relational encoding correlates positively with the activity of the anterior medial temporal lobe regions.

Aged↗

Hemispheric activation of anterior and inferior prefrontal cortex during verbal encoding and recognition: a PET study of healthy volunteers.

Evidence of bilateral prefrontal activation during memory encoding and retrieval has increased attention given to anatomical subdivisions within the prefrontal cortex. The current study examined anterior and inferior aspects of the prefrontal cortex to determine their degree of functional and hemispheric overlap during encoding and recognition. Cerebral blood flow of 25 healthy volunteers was measured using PET (15)O-water methods during four conditions: resting baseline, sequential finger movement, word encoding, and word recognition. Resting and motor images were averaged to provide a single reference that was subtracted from encoding and recognition using statistical parametric mapping (SPM96). Memory conditions were also subtracted from each other to identify differences in regional activity. Subjects performed well (86% correct) and had a slightly conservative response bias. Baseline subtraction from encoding revealed focal activation of left inferior prefrontal cortex (area 45) without significant contralateral activation. Recognition minus baseline subtraction produced a focal right anterior prefrontal activation (areas 9 and 10) that was not present in the left hemisphere. Bilateral effects were seen in area 45 during recognition. Subtraction of memory tasks from each other did not reveal any areas of greater activity during encoding. However, the recognition task produced greater activation in right area 9 extending into the anterior cingulate. Greater activity during recognition was also observed in left insula and bilateral visual integration areas. These results are discussed in relation to the prevailing model of prefrontal hemispheric asymmetry during episodic memory.

Adult↗

Distinct neural systems for the encoding and recognition of topography and faces.

In a series of three positron emission tomography experiments the functional neuroanatomy of four different types of visual stimuli was investigated within the same experimental context. The stimuli were unknown buildings, landscapes, human faces, and animal faces. The purpose of the present study was to compare the stimulus types, both within the same category and across category, by examining if, at encoding (with several seconds exposure to each stimulus) or recognition (over time scales of minutes compared to the seconds of usual perception/one-back studies), common or different neural circuits were activated for all types/categories of stimuli. Within category and although visually very different, the encoding of both buildings and landscapes activated a similar set of brain regions, including bilateral parahippocampal gyrus. This was in contrast to the encoding of both human and animal faces, both of which resulted in activation of the fusiform gyrus bilaterally. Despite the perceptual inputs being identical to those during encoding, the recognition of both buildings and landscapes activated only unilateral right parahippocampal gyrus, while recognition of both human and animal faces activated unilateral right fusiform gyrus. In addition, right superior frontal gyrus and right inferior and medial parietal areas were more active during recognition compared with encoding for all stimulus types. Overall the data identify differential patterns of activation for encoding compared with retrieval of visual stimuli. Furthermore, medial temporal structures specifically are involved in the explicit learning and long-term recognition of topographically relevant stimuli, be they buildings or landscapes, while lateral temporal structures support nontopographical learning and recognition, in this case either human or animal faces.

Adult↗

Anterior medial temporal lobe activation during attempted retrieval of encoded visuospatial scenes: an event-related fMRI study.

Various studies have shown that the medial temporal lobe (MTL), which consists of the hippocampus and parahippocampal gyrus, is important for episodic memory. Earlier fMRI studies substantiated this role by showing activation upon encoding of visuospatial scenes. In this study we used event-related fMRI to study whether the cognitive process of retrieval of visuospatial scenes, tested with the use of a recognition paradigm, also activates the MTL. Nine subjects (mean age 24 years) were presented previously studied color pictures (old) and pictures they had never seen before (new) in a mixed trial design. Data analysis allowed calculation of the fMRI response of correct judgments on new pictures, old pictures, and false judgments. Since we used previously encoded color pictures as old stimuli, we also included an encoding paradigm in the current set of experiments. This allowed us to compare encoding and recognition activation in the MTL of exactly the same pictures in the same subjects. Correct judgments on new pictures showed an increased activation in the anterior parahippocampus bilaterally and the right anterior hippocampus compared to judgments on old pictures in the recognition experiment. The former judgments took significantly longer, indicating that retrieval of successfully stored information is less demanding than the effort to retrieve nonencoded information. A comparison of the two experimental data sets showed evidence for a functional segregation of encoding and retrieving color pictures. We conclude that the left posterior parahippocampal gyrus responds during encoding, while on the other hand the left anterior parahippocampal gyrus and the right anterior hippocampus were more strongly involved in retrieval.

Adult↗