Regional differentiation of neuron morphology in human left and right hippocampus: Comparing normal to schizophrenia

Regional differentiation based on size, form, and orientation angle of the soma of individual neurons in human post-mortem hippocampus was determined through correlations between pairs of hippocampal subfields in each side separately. The neurons were previously measured on a computer. In the normal cases, a left-right asymmetrical pattern of regional differentiation based on soma size emerged, while for form and orientation angle, the patterns appeared symmetrical. In schizophrenia, regional soma size, form, and orientation variability were expressed largely symmetrically. Regional correlations based on neuronal density revealed an asymmetrical hemispheric pattern in the normal cases versus a nearly symmetrical pattern in schizophrenia. Taken together, the inter-regional correlations favor a hippocampal landscape that deviates in each side from connectivity based on the canonical trisynaptic hippocampal circuitry. It is proposed that during morphogenesis, rudimentary inter-regional networks are formed through specific interactions between regional neurons; these networks are present in the adult hippocampus and may be vulnerable in brain diseases

Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils

The time course of oxidative damage in different brain regions was investigated in the gerbil model of transient cerebral ischemia. Animals were subjected to both common carotid arteries occlusion for 5 min. After the end of ischemia and at different reperfusion times (2, 6, 12, 24, 48, 72, 96 h and 7 days), markers of lipid peroxidation, reduced and oxidized glutathione levels, glutathione peroxidase, glutathione reductase, manganese-dependent superoxide dismutase (MnSOD) and copper/zinc containing SOD (Cu/ZnSOD) activities were measured in hippocampus, cortex and striatum. Oxidative damage in hippocampus was maximal at late stages after ischemia (48-96 h) coincident with a significant impairment in glutathione homeostasis. MnSOD increased in hippocampus at 24, 48 and 72 h after ischemia, coincident with the marked reduction in the activity of glutathione-related enzymes. The late disturbance in oxidant-antioxidant balance corresponds with the time course of delayed neuronal loss in the hippocampal CA1 sector. Cerebral cortex showed early changes in oxidative damage with no significant impairment in antioxidant capacity. Striatal lipid peroxidation significantly increased as early as 2 h after ischemia and persisted until 48 h with respect to the sham-operated group. These results contribute significant information on the timing and factors that influence free radical formation following ischemic brain injury, an essential step in determining effective antioxidant intervention

Occasional essay: upper motor neuron syndrome in amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) requires recognition of both lower (LMN) and upper motor neuron (UMN) dysfunction.1 However, classical UMN signs are frequently difficult to identify in ALS.2 LMN involvement is sensitively detected by electromyography (EMG)3 but, as yet, there are no generally accepted markers for monitoring UMN abnormalities,4 the neurobiology of ALS itself, and disease spread through the brain and spinal cord,.5 Full clinical assessment is therefore necessary to exclude other diagnoses and to monitor disease progression. In part, this difficulty regarding detection of UMN involvement in ALS derives from the definition of ‘the UMN syndrome’. Abnormalities of motor control in ALS require reformulation within an expanded concept of the UMN, together with the neuropathological, neuro-imaging and neurophysiological abnormalities in ALS. We review these issues here

Alterations in white matter microstructure in neurofibromatosis-1.

Neurofibromatosis (NF1) represents the most common single gene cause of learning disabilities. NF1 patients have impairments in frontal lobe based cognitive functions such as attention, working memory, and inhibition. Due to its well-characterized genetic etiology, investigations of NF1 may shed light on neural mechanisms underlying such difficulties in the general population or other patient groups. Prior neuroimaging findings indicate global brain volume increases, consistent with neural over-proliferation. However, little is known about alterations in white matter microstructure in NF1. We performed diffusion tensor imaging (DTI) analyses using tract-based spatial statistics (TBSS) in 14 young adult NF1 patients and 12 healthy controls. We also examined brain volumetric measures in the same subjects. Consistent with prior studies, we found significantly increased overall gray and white matter volume in NF1 patients. Relative to healthy controls, NF1 patients showed widespread reductions in white matter integrity across the entire brain as reflected by decreased fractional anisotropy (FA) and significantly increased absolute diffusion (ADC). When radial and axial diffusion were examined we found pronounced differences in radial diffusion in NF1 patients, indicative of either decreased myelination or increased space between axons. Secondary analyses revealed that FA and radial diffusion effects were of greatest magnitude in the frontal lobe. Such alterations of white matter tracts connecting frontal regions could contribute to the observed cognitive deficits. Furthermore, although the cellular basis of these white matter microstructural alterations remains to be determined, our findings of disproportionately increased radial diffusion against a background of increased white matter volume suggest the novel hypothesis that one potential alteration contributing to increased cortical white matter in NF1 may be looser packing of axons, with or without myelination changes. Further, this indicates that axial and radial diffusivity can uniquely contribute as markers of NF1-associated brain pathology in conjunction with the typically investigated measures

The charm of structural neuroimaging in insanity evaluations. guidelines to avoid misinterpretation of the findings

Despite the popularity of structural neuroimaging techniques in twenty-first-century research, its results have had limited translational impact in real-world settings, where inferences need to be made at the individual level. Structural neuroimaging methods are now introduced frequently to aid in assessing defendants for insanity in criminal forensic evaluations, with the aim of providing “convergence” of evidence on the mens rea of the defendant. This approach may provide pivotal support for judges’ decisions. Although neuroimaging aims to reduce uncertainty and controversies in legal settings and to increase the objectivity of criminal rulings, the application of structural neuroimaging in forensic settings is hampered by cognitive biases in the evaluation of evidence that lead to misinterpretation of the imaging results. It is thus increasingly important to have clear guidelines on the correct ways to apply and interpret neuroimaging evidence. In the current paper, we review the literature concerning structural neuroimaging in court settings with the aim of identifying rules for its correct application and interpretation. These rules, which aim to decrease the risk of biases, focus on the importance of (i) descriptive diagnoses, (ii) anatomo-clinical correlation, (iii) brain plasticity and (iv) avoiding logical fallacies, such as reverse inference. In addition, through the analysis of real forensic cases, we describe errors frequently observed due to incorrect interpretations of imaging. Clear guidelines for both the correct circumstances for introducing neuroimaging and its eventual interpretation are defined