**1. Introduction**

14 Neuroimaging for Clinicians – Combining Research and Practice

Matsui M, Imamura T, Sakamoto S, Ishii K, Kazui H, Mori E. Transient global amnesia:

Moscovitch M. In: Memory Distortion: How minds, Brains, and Societies Reconstruct the

Miller SL, Fenstermacher E, Bates J, Blacker D, Sperling RA, Dickerson BC. Hippocampal

Naeser M, Palumbo C, Helm-Estabrooks N. Severe nonfluency in aphasia: role of the medial

Nardone R, Buffone EC, Matullo MF, Tezzon F. Motor cortex excitability in transient global

Neisser U. Cognitive Psychology. New York: Appleton-Century-Crofts; 1967, ISBN

Nitrini R, Buchpiguel CA, Caramelli P, Bahia VS, Mathias SC, Nascimento CM, Degenszajn

parietotemporal hypoperfusion. Acta Neurol Scand. 2000 Mar;101(3):172-6. Peres JF, McFarlane A, Nasello AG, Moores KA. Traumatic memories: bridging the gap

Petersen SE, Fox PT, Posner MI, Mintun M, Raichle ME. Positron emission tomographic

Rajah MN, D'Esposito M. Region-specific changes in prefrontal function with age: a review

Schacter DL, Reiman E, Curran T, Yun LS, Bandy D, McDermott KB, Roediger HL.

Schacter DL. Illusory memories: a cognitive neuroscience analysis.Proc Natl Acad Sci U S A.

Sperling R. Functional MRI studies of associative encoding in normal aging, mild cognitive impairment, and Alzheimer's disease. Ann NY Acad Sci. 2007;1097:146–155. Vannini P, Almkvist O, Dierks T, Lehmann C, Wahlund LO. Reduced neuronal efficacy in

Warren JD, Chatterton B, Thompson PD. A SPECT study of the anatomy of transient global

from positon emission tomography. Neuron. 1996;17:267–274.

processing. Psychiatry Res. 2007;156:43–57.

amnesia, J Clin Neurosci 7 (2000), pp. 57–59.

magnetic resonance imaging, Neuroradiology 44 (2002), pp. 235–238. Mazziotta JC, Phelps ME.. Human sensory stimulation and deprivation: positron emission

tomographic results and strategies. Ann Neurol 1984;15:S50-S60

decline. J Neurol Neurosurg Psychiatry. 2008;79:630–635.

ISBN 0674566769.

0521485002.

2008;42(6):478-88.

(Pt 9):1964-83.

1996;93(24):13527-33.

speech. Brain 1989;112:1-38.

amnesia. J Neurol 251 (2004), pp. 42–46.

increased signal intensity in the right hippocampus on diffusion-weighted

Past. Schacter D L, editor. Cambridge, MA: Harvard Univ. Press; 1997. pp. 226–254.

activation in adults with mild cognitive impairment predicts subsequent cognitive

subcallosal fasciculus plus other white matter pathways in recovery of spontaneous

J, Caixeta L. SPECT in Alzheimer's disease: features associated with bilateral

between functional neuroimaging and psychotherapy.Aust N Z J Psychiatry.

studies of the cortical anatomy of single word processing. Nature 1988;331:585-589.

of PET and fMRI studies on working and episodic memory. Brain. 2005 Sep;128

Neuroanatomical correlates of veridical and illusory recognition memory: evidence

progressive mild cognitive impairment: A prospective fMRI study on visuospatial

Neurodegenerative diseases are progressive, hereditary or sporadic diseases of the nervous system. Progressive neurodegeneration causes i.e. loss of movement ability like in motor neuron diseases or cognitive deficits like in dementia. Despite the fact that many similarities appear on the sub-cellular level that relate different neurodegenerative diseases with each other, the broad variety on the clinical level remains which causes major demands both in clinical care and daily living.

Advances in neuroimaging have led to an extensive application of this technique in clinical and scientific studies. Neuroimaging is a non-invasive approach of measuring either structural properties or activity of the brain. Activity of the brain can be investigated during defined tasks or during rest to observe functional connectivity of cortical and subcortical regions in time and space. Neuroimaging in neurodegenerative diseases has extensively increased our understanding of interaction of functional executive decline e.g. in movement and cognition and of changes in cortical pattern activity. Neuroimaging is a promising candidate for an objective marker for e.g. drug efficacy. By these means, neuroimaging as a biomarker can improve predictability of outcome in clinical trials. Furthermore, discovering patterns of vulnerability of neurons on the cortical and subcortical level helps to disentangle the course of degeneration in different diseases in vivo to support post-mortem findings. Those ex-vivo analyses had been the only means to get an understanding of disease courses before neuroimaging evolved.

The following article will give an introduction to the characteristics of the main neurodegenerative diseases and techniques that have been used in understanding pathogenesis and aetiology of neurodegenerative diseases. It encompasses main findings in structural and functional neuroimaging in Motor Neuron Diseases (MND) and in others like dementias, Parkinson's disease (PD) and Huntington's disease.

With our work we mainly focused on Motor Neuron Diseases like ALS and we provided clear evidence for pathological involvement of areas extending the motor system like emotional and sensory processing pathways. Overall, the article will highlight the capacity of neuroimaging to shed light onto aetiology and pathogenesis of neurodegeneration in the human central nervous system.

Degeneration of the Human Nervous System and Magnetic Resonance Neuroimaging 17

Alzheimer's disease (AD) is the most common form of dementia. It is named after the German psychiatrist and neuropathologist Alois Alzheimer who first described the disease in the early 20th century. The other most common form of dementia is vascular dementia. Some other forms are dementia with Lewy bodies, and frontotemporal lobal degeneration, which is subdivided into the behavioural variant (fronto-temporal dementia, FTD), the semantic dementia, primary progredient aphasia, corticobasal degeneration, progressive supranuclear palsy and amyotrophic lateral sclerosis with frontotemporal dementia. Numerous other neurodegenerative illnesses have an associated dementia, including Creutzfeldt–Jakob disease, Huntington's disease, multiple system atrophy, and Parkinson's

dementias are acquired diseases that clinically affect cognitive abilities and daily activities. Classification of dementias can be done according to different criteria: cortical (memory, language, thinking and social skills are affected) and subcortical pathology (emotional processing, movement and memory are primarily affected). Furthermore, it can be classified according to whether it is a progressive form (cognitive abilities worsen over time), and whether it is primary (results from a specific disease such as Alzheimer's disease) or secondary (occurs because of disease or injury like vascular dementia). Patho-anatomical hallmark is the degeneration of the brain (mainly frontal and temporal areas). Early stages of dementia are often mistakenly considered as normal aging problems like forgetfulness and memory storage problems. With the means of standardised diagnostic tools problems in memory, language (aphasia), attention, planning and concept formation, psychomotor

Due to the changing demographics in western countries, the incidence of dementias constantly increases. About 5-10% of the people >65 years and 30-40% of those above 80 develop dementias. Incidence increases exponentially with age. Women are more often

The cause of Alzheimer's disease is not fully understood. There are several hypotheses, which have different supporters. The most widely used hypothesis is the amyloid hypothesis. Amyloid beta deposits are found in the brain of AD patients preceding the onset of clinical dementia. However, amyloid beta is not pathological per se and is found in healthy aged people. Furthermore, amyloid plaque deposition do not correlate with neuron loss and also not with clinical symptoms. Abnormally phosphorylated tau protein may start quite early, i.e., before puberty or in early young adulthood and therefore decades before

Parkinson's disease is the second most common degenerative disease of the central nervous system. Pathological hallmark of the idiopathic Parkinson's syndrome are movement related symptoms like slowness of movements, rigidity and tremor. Subtypes distinguish between the predominance of symptoms in a patient. Changes in mood and cognitive deficits are described as non-motor symptoms in PD. In late stage PD dementia is a common hallmark. Like ALS, PD affects people in midlife. However, there is evidence that disease process starts early in life (Braak & Del Tredici 2011b). The disease is caused by death of

**3.2 Disease of the central nervous system** 

disease dementia (Tartaglia et al.,2011).

function and personality problems can be detected.

clinical onset of the disease (Braak & Del Tredici, 2011b).

**3.2.2 Parkinson's Disease (PD)** 

**3.2.1 Dementias** 

affected than men.
