Topological Biomarker of Alzheimer’s Disease

For years, it has been assumed that the cerebral accumulation of pathologic protein forms is the main trigger of Alzheimer’s disease (AD) pathology; however, recent studies revealed strong evidences that the alternations in synaptic activity precede and affect the homeostasis of amyloid-beta and tau, both of which aggregate during AD. Given that the neuropathological changes, characteristic for AD, start decades before the onset of the first symptoms, when alternations become irreversible, it is crucial to find a biomarker that can detect the preclinical signs of disease, presumably synaptic dysfunction of specific cerebral areas. Here is presented a novel, a high potential neuroimaging biomarker that can detect the postsynaptic dysfunction of specific neural substrate located in medial prefrontal cortex (mPFC) during sensory gating processing of a simple auditory stimulus. The magnetoencephalography-based localization of mPFC gating activation has the potential not only to detect symptomatic AD but also to become a predictor of cognitive decline related to the pathophysiological processes of AD, both at the individual level. The strengths of proposed biomarker lie in the simplicity of using a binary value, i.e., activated or not activated a neural generator along with its potential to follow the evolution of the pathophysiological process of disease from preclinical phase. The novel biomarker does not require estimation of uniform cutoff levels and standardization processes, the main problems of so far proposed biomarkers. Ability to individually detect AD pathology during putative preclinical and clinical stages, absolute noninvasiveness, and large effect size give this biomarker a high translation capacity and clinical potential

Early Attentional Modulation of the Neural Network Evoked with the Auditory Paired-click Paradigm: An MEG Study

AbstractAlthough numerous research studies have explored the functional attributes of the human duration perception, the spatio- temporal information on cortical networks underlying this process is still an open question. Moreover, the issue of possible differences in the nature of timing mechanisms responsible for perception of sub- and supra-second intervals requires the implementation of the functional brain imaging techniques with both high spatial and temporal resolution. Attention is very frequently used as a modulating factor for the perceived duration of a sensory stimulus. The non-attended stimuli appear to last shorter than the attended ones, increasing the perceived duration of a concurrent stimulus (Gorea, 2011). This study challenges the accepted model of early sensory responses, activated during the first 100ms after stimulus presentation, as preattentive, automatic processes which modulate the neural sensitivity to incoming stimuli (gating phenomena). We utilized Elekta Neuromag 306-channel whole-head system for magnetoencephalography (MEG) measurements and multi-dipole Calibrated Start Spatio Temporal (CSST) localization technique (Ranken et al., 2002) to investigate whether voluntary attention directed at the second tone of a pair in the standard paired-click paradigm could affect cortical networks underlying the gating out phenomenon. MEG recordings were obtained in a magnetically shielded room at the Biomagnetic Center in Jena, Germany. Two consecutive (ISI=500ms) identical short tonnes (S1 and S2; duration=20ms; f=1200Hz; ITI=8±1s) were used to evoke standard gating cortical responses in 19 healthy participants (21-38 years). In the second condition, the task was to direct attention toward the second tone and to respond to a rarely presented non-identical second tone of the pair (R=1300Hz, p(S1R)=0.3). MEG recordings showed transient early and middle latency responses with peak amplitudes over the temporo-parietal sensors followed by a peak of a sustained activity. Less prominent transient activity was recorded over the frontal sensors, accompanied with a more steady- state component from 100 until 400ms post-stimulus for both conditions. Preliminary results of the CSST spatio-temporal analyses revealed 4-6 brain regions activated during 20-500ms time interval including bilateral superior temporal gyrus (STG), bilateral and medial prefrontal (PF), bilateral parietal (PA) regions, and central motor cortex area. A cortical source underlying the steady-state component was identified in the left prefrontal region for S1 tone, and in central posterior regions (PA) for the repeated tone S2. During the standard paradigm the M50 gating suppression was observed only for bilateral STG sources while bilateral PF and PA sources did not show any reduction in the response during the first 100ms post-stimulus. Targeting the attention towards the second tone enhanced the M50 amplitude of the bilateral STG responses in respect to the repeated stimulus S2 and caused a change in the activated network evident by the emergence of a new generator in the medial PF area (orbitofrontal) instead of dorsolateral PF generators evoked in non-attended condition. These results demonstrate that voluntary attention can exert a topological and functional modulatory influence on the neural network even during early stages of auditory processing

Neuroimaging - Structure, Function and Mind

Neuroimaging provides a valuable noninvasive window into the human neural system and is used in fundamental and clinical research. Imaging techniques are essential for understanding spontaneous neural activity and brain mechanisms engaged in the processing of external inputs, memory formation, and cognition. Modern imaging modalities make it possible to visualize memory processes within the brain and to create images of its structure and function. Scientists and technologists are joining forces to pave the way for improving imaging technologies and methods, data analysis, and the application of imaging to investigate the wide spectra of neurological diseases, neuropsychological disorders, and aging. Imaging techniques are essential for the identification of biological markers of the earliest stages of neurodiseases and the development of new therapies. This book intends to provide the reader with a short overview of the current achievements in the state-of-the-art imaging modality methods, their highlights, and limitations in neuroscience research and clinical applications. The current state of in-vivo neuroimaging methods in the context of the understanding and diagnosis of mental disorders and relation to the mind is also discussed in a modern compact format, featuring the latest and most relevant research results