Pathological changes in the primary visual cortex (Area V1) in Creutzfeldt-Jakob syndrome

About 10% of patients with Creutzfeldt-Jakob syndrome (disease) (CJD) exhibit visual symptoms at presentation and approximately 50% during the course of the disease. The objectives of the present study were to determine, in two subtypes of CJD, viz., sporadic CJD (sCJD) and variant CJD (vCJD), the degree of pathological change in the primary visual cortex (area V1) and the extent to which pathology in V1 may influence visual function. The vacuolation (‘spongiform change’), surviving neurons, glial cell nuclei, and deposits of prion protein (PrP) were quantified in V1 obtained post-mortem in nine cases of sCJD and eleven cases of vCJD. In sCJD, the vacuoles and PrP deposits were regularly distributed along the cortex parallel to the pia mater in clusters with a mean dimension from 450 to 1000 µm. Across the cortex, the vacuolation was most severe in laminae II/III and the glial cell reaction in laminae V/VI. Surviving neurons were most abundant in laminae II/III while PrP deposition either affected all laminae equally or was maximal in lamina II/III. In vCJD, the vacuoles and diffuse PrP deposits were distributed relatively uniformly parallel to the pia mater while the florid deposits were consistently distributed in regular clusters. Across V1, the vacuoles either exhibited a bimodal distribution or were uniformly distributed. The diffuse PrP deposits occurred most frequently in laminae II/III while the florid deposits were more generally distributed. The data suggest that in both sCJD and vCJD, pathological changes in area V1 may affect the processing of visual information in laminae II/III and its transmission from V1 to V2 and to subcortical visual areas. In addition, the data suggest an association in sCJD between the developing pathology and the functional domains of V1 while in vCJD the pathology is more uniformly distributed. These changes could be a factor in the development of poor visual acuity, visual field defects, cortical blindness, diplopia, and vertical gaze palsy that have been observed in Creutzfeldt-Jakob syndrome.

Is there a spatial association between senile plaques and neurofibrillary tangles in Alzheimer's disease?

Objective: To test the hypothesis that the clusters of senile plaques (SP) and neurofibrillary tangles (NFT) in patients with Alzheimer's disease (AD) are spatially associated as predicted by the 'Amyloid Cascade Hypothesis'. Methods: The spatial association between the SP and NFT was studied in the cerebral cortex and hippocampus in six cases of sporadic Alzheimer's disease (AD) using contingency tables. The coefficient C7 was used as an index of spatial association while chi-square with correction for continuity was used as a test of significance. Results: In the brain regions analysed, values of C7 were in the range -0.31 to +0.32 but a statistically significant spatial association between SP and NFT was present in only 8/39 (21%) regions. The degree of spatial association between the SP and NFT was similar in dfferent brain regions and did not vary with apolipoprotein ε genotype of the patient. However, the magnitude of C7 in a region was positively correlated with the density of the NFT and with the total density of SP and NFT but not with the density of SP alone. Conclusion: There was little evidence that SP and NFT were spatially associated except in brain areas with high densities of lesions. The data support the hypothesis that SP and NFT are distributed relatively independently in the cerebral cortex and hippocampus and therefore, could be distinct phenomena in AD.

Pathological changes in the primary visual cortex (area V1) in sporadic Creutzfeldt-Jakob disease

Purpose. To determine the degree of pathological change in the primary visual cortex (area V1) in patients with Creutzfeldt-Jakob disease. Method. The vacuolation, surviving neurons, glial cells, and deposits of prion protein were quantified in area V1 obtained postmortem in nine cases of the sporadic type of Creutzfeldt-Jakob disease. Results. Variations in the density of glial cells and in prion protein deposition were particularly evident between patients. In the upper and lower cortical laminae, vacuoles and prion protein deposits were regularly distributed in clusters with a mean dimensions of 450 to 1000 µm. Vacuolation in area V1 was most severe in lamina III and the glial cell reaction in lamina V or VI. Surviving neurons were most abundant in lamina II or III, whereas prion protein deposition either affected all laminae equally or was maximal in lamina II or III. Conclusion. The data suggest that pathological changes in area V1 in sporadic type of Creutzfeldt-Jakob disease may affect the transmission of visual information from area V1 to V2 and to subcortical visual areas. In addition, the data suggest an association between the developing pathology and the functional domains of area V1.

Investigating the functional properties of the somatosensory cortex during experimental visceral pain using magnetoencephalography

Background The somatosensory cortex has been inconsistently activated in pain studies and the functional properties of subregions within this cortical area are poorly understood. To address this we used magnetoencephalography (MEG), a brain imaging technique capable of recording changes in cortical neural activity in real-time, to investigate the functional properties of the somatosensory cortex during different phases of the visceral pain experience. Methods In eight participants (4 male), 151-channel whole cortex MEG was used to detect cortical neural activity during 25 trials lasting 20 seconds each. Each trial comprised four separate periods of 5 seconds in duration. During each of the periods, different visual cues were presented, indicating that period 1=rest, period 2=anticipation, period 3=pain and period 4=post pain. During period 3, participants received painful oesophageal balloon distensions (four at 1 Hz). Regions of cortical activity were identified using Synthetic Aperture Magnetometry (SAM) and by the placement of virtual electrodes in regions of interest within the somatosensory cortex, time-frequency wavelet plots were generated. Results SAM analysis revealed significant activation with the primary (S1) and secondary (S2) somatosensory cortices. The time-frequency wavelet spectrograms showed that activation in S1 increased during the anticipation phase and continued during the presentation of the stimulus. In S2, activation was tightly time and phase-locked to the stimulus within the pain period. Activations in both regions predominantly occurred within the 10–15 Hz and 20–30 Hz frequency bandwidths. Discussion These data are consistent with the role of S1 and S2 in the sensory discriminatory aspects of pain processing. Activation of S1 during anticipation and then pain may be linked to its proposed role in attentional as well as sensory processing. The stimulus-related phasic activity seen in S2 demonstrates that this region predominantly encodes information pertaining to the nature and intensity of the stimulus.

Oscillatory beta activity mediates neuroplastic effects of motor cortex stimulation in humans

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibithumanmotor cortex (M1) excitability and impair movement for ≤1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15-35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function. © 2013 the authors.