Biomedical subjects

S McInerney

Publications and source records attributed to S McInerney.

4 recordsLinked to original sources

PubMed2004

Holoprosencephaly--topologic variations in a liveborn series: a general model based upon MRI analysis.

We present an MRI-based anatomic analysis of a series of 9 human brains, representing lobar, semilobar and alobar forms of holoprosencephaly. The analysis of these variable forms of the malformation is based upon a topologic systematics established in a prior analysis of a homogeneous set of semilobar malformations. This systematics has the dual advantage that it serves both as a uniform reference for qualitative description and as a quantitative descriptive base for mathematical correlations between parameters of topology and of growth and development. Within this systematics, the prosencephalic midline is divided from caudal to rostral into diencephalic (DD-right and left, subthalamus through suprachiasmatic junction with telencephalon), telencephalic (TT-right and left, suprachiasmatic border of telencephalon midline to hippocampal commissure) and diencephalic-telencephalic (DT-right and left-hippocampal commissure through temporal limb of choroid fissure) segments. The topologic abnormality of the initial semilobar series was expressed in an orderly rostral to caudal gradient along the TT segment. In each malformation, normal midline topology began with a small posterior corpus callosum. Although the topologic anomaly in the present series invariably also involved the TT segment, this involvement was not continuous and was variably associated with anomalies of the DD in 6 and unilaterally of the DT in 1 brain. In the present as well as with the earlier series of HPE malformations but not in "normative brains," total telencephalic growth is strongly correlated with the length of the midline telencephalic segment. We propose that this system of analysis will be sensitive to the developmental stage and locus of expression of genetic and non-genetic determinants of the formal origin of HPE. For all of the present series, karyotype anlyses were normal. Mutations in the Shh and Zic2 genes were excluded in 2 cases.

Brain↗

PubMed2003

Semilobar holoprosencephaly with midline 'seam': a topologic and morphogenetic model based upon MRI analysis.

We present an MRI-based anatomic analysis of a series of seven human brains with the semilobar form of holoprosencephaly. The analysis defines a set of common descriptors for a pattern of topological anomaly which is uniform for the set of seven brains. The core of the anomaly is a rostro-caudally aligned midline gray matter 'seam' that extends from the telencephalic-suprachiasmatic junctional region to abut the posterior aspect of the callosal commissure. The seam forms the ventricular roof throughout its extent. Rostrally it is formed by the conjoined heads of caudate/accumbens nuclei. It continues caudally as a gray matter bridge in the fundus of the interhemispheric fissure, where it bridges right and left neocortex. Fornix, septal nuclei and septal limb of the choroid plexus are absent, and the telencephalic ventricles communicate with the diencephalic via open septal limbs of the choroid fissures. By contrast, the temporal limb of hippocampal formation and the choroid plexus are normal and the temporal limb of the choroid fissure is closed. This topological anomaly of conjoined left and right cortical and nuclear gray matter into a midline seam and absent septal structures is thus confined to the region of the midline telencephalic hemisphere evagination. Total telencephalic growth is strongly correlated with the length of this topologically abnormal midline telencephalic segment. The set of findings is consistent with graded failure of induction of rostral to caudal specification in the midline rostral telencephalic zone.

Aging↗

PubMed1998

Thalamic deactivation during early implicit sequence learning: a functional MRI study.

Previous research has implicated the striatum in implicit sequence learning. However, imaging findings have been inconsistent with regard to activity within the thalamus during performance of such tasks. Contemporary models of cortico-striato-thalamic circuitry suggest opposing influences on thalamic activity; suppression of thalamic activity is mediated by the indirect pathway and enhancement is mediated by the direct pathway. Using functional magnetic resonance imaging, we studied activity within human thalamus during early and late phases of an implicit sequence learning task known to reliably recruit the striatum. Significant deactivation (decreased signal relative to a baseline condition) was observed within the thalamus during early implicit learning. This finding is consistent with models of cortico-striato-thalamic function and specifically supports a profile of early 'thalamic gating' via the indirect pathway.

Basal Ganglia↗

PubMed1997

II. Localization and characterization of dopamine D4 binding sites in rat and human brain by use of the novel, D4 receptor-selective ligand [3H]NGD 94-1.

The dopamine D4 selective ligand, [H]NGD 94-1, was used in these studies to characterize binding sites in rat and human brain tissue by membrane binding and autoradiography techniques. Autoradiographic analysis of rat brain showed that specific [3H]NGD 94-1 binding was greatest in entorhinal cortex, lateral septal nucleus, hippocampus and the medial preoptic area of the hypothalamus. This nonstriatal distribution of [3H]NGD 94-1 binding was distinct from the autoradiographic distribution of dopamine D2 and D3 receptor subtypes. In homogenate preparations from rat brain regions, [3H]NGD 94-1 binding sites were low in density (<30.0 fmol/mg protein). The low density of D4 binding sites was corroborated by autoradiographic comparisons in which binding density for D4 receptors as measured by [3H]NGD 94-1 was only 1/7 of D2 and 1/5 of D3 receptor densities, despite corrections for differing radioligand binding characteristics. Pharmacological evaluation showed high affinity at rat [3H]NGD 94-1 binding sites for compounds with known D4 receptor affinity and little displacement by compounds with affinity for dopamine D1/D2/D3 receptor subtypes. Specific, high-affinity [3H]NGD 94-1 binding was also present in several human brain regions, including hippocampus, hypothalamus, dorsal medial thalamus, entorhinal cortex, prefrontal cortex and lateral septal nucleus. High-affinity [3H]NGD 94-1 binding was not present in any human striatal region examined. The pharmacological profile of [3H]NGD 94-1 binding sites in human brain was consistent with that previously demonstrated for cloned human D4 receptors expressed in mammalian cells. These findings suggest that specific, high-affinity [3H]NGD 94-1 binding exists in rat and human brain and that these sites reflect populations of dopamine D4 receptors with a distribution unique among dopamine receptor subtypes.

Animals↗