What's the/is there a relation between neurodegeneration and cerebral reorganisation?
1. Interaction of neurodegeneration and cerebral reorganisation
1.1. how do the mechanisms which cause neurodegeneration impact cerebral reorganisation?
1.1.1. Cerebral reorganization in Parkinson’s disease Rick Helmich
1.1.1.1. The disfunction of the striatum affects the healthy cerebello-thalamic circuits which actually produce the resting tremmor.
1.1.1.1.1. The cerebello-thalamic interacts in the thalamus with the thalamo-sensory cortex tracts.
1.1.1.2. The miss-interpretation of somatosensory information caused by the influence of broken pallido-thalamic tracts over healthy thalamo-cortical tracts.
1.1.1.2.1. The sensory processing is driven in a "tremorous state" in which cyclical oscillations interrupt normal neuronal activity patterns.
1.1.1.3. increase in neuron sinergism inside the striatum due to the loss of Dopamine.
1.1.1.3.1. Blurring the connection between cognitive and motor processing
1.1.1.3.2. Blurring the somatotopy within motor loop
1.2. is there an impact of i.g. iron or alpha-synucleine in reorganisation?
1.3. Causes of neurodegeneration
1.3.1. http://www.ncbi.nlm.nih.gov/pubmed?term=17372132
1.3.1.1. acceleration of cell loss in the SNc, causing nigrostriatal degeneration to both reach a threshold for symptoms in advance of earlier affected brain areas and progress more rapidly than other aspects of the disease
1.4. functional pathways that are lost with the degeneration of the striatum
1.4.1. Cerebral reorganization in Parkinson’s disease Rick Helmich
1.4.1.1. altered connection with primary and secondary Somato-Sensory cortex (impairment in the perception of body's position in space)
1.4.1.2. altered connection with the Pre Motor Area
1.4.1.3. Skin deafferentation proven by skin byopsies and quantitative sensory testing
1.5. interaction between brain areas
1.5.1. Cerebral reorganization in Parkinson’s disease Rick Helmich
1.5.1.1. The somatosensory processing is altered by motor imagery tasks.
1.5.1.2. Because the Putamen doesn't work distorted sensory maps are sent to premotor area.
2. Are there predictive factors for a good compensation of neurodegeneration?
2.1. sex,age
2.2. Type (genetic, idiopathic or toxic)
2.3. Motivation, good cognitive control
2.3.1. Cerebral reorganization in Parkinson’s disease Rick Helmich
2.3.1.1. The Anterior Cingulate Cortex is an area where motor, motivational and cognitive loops can interract
2.4. What are the brain differences between PD patients who compensate and those who not?
2.4.1. Cerebral reorganization in Parkinson’s disease Rick Helmich
2.4.1.1. Patients least affected with their motor control of an assymetric affected hand do better on visual processing. (the strengthening of occipito-parietal connections)
2.4.1.2. markedly increase in the power of somatosensory cortex to gather data from other sources
2.5. forms of clinical Parkinson
2.5.1. Cerebral reorganization in Parkinson’s disease Rick Helmich
2.5.1.1. Patient with tremor-dominant symptoms do clinically better because they use their tremor as somatosensory cueing. (role of VIM nucleus in the thalamus)
2.6. Psychological State
2.6.1. Depression
2.6.1.1. Cerebral reorganization in Parkinson’s disease Rick Helmich
2.6.1.1.1. Depression decreases motor control by lowering Dopamine levels in the Ventral Putamen and decreasing serotoninergic function.
3. How does cerebral reorganisation work?
3.1. Are there any brain areas more prone to organisation than others?
3.1.1. "Cerebral reorganization in Parkinson’s disease" Rick Helmich
3.1.1.1. The Remapping happens between Parietal lobe and Pallidum and it can be predicted by the dopamine content heterogenity in the Pallidum
3.1.1.2. enhancement in the Cingulate Motor Area
3.2. Is there a connection to the stages of the disease?
3.2.1. Hoehn & Yahr Clinical staging
3.2.2. Braak stages of Lewy Body progression patterns
3.3. Is there an active learning process involved or does it happen involuntary?
3.3.1. "Cerebral reorganization in Parkinson’s disease" Rick Helmich
3.3.1.1. The motivational modulation of cognitive control depends on the dopamine in the striatum and it can be improved by the expectation of a reward.
3.4. What compensation mechanisms are there besides motor compensation?
3.5. Can the number of neuronal progenitor cells (NPC) inside the patient's brain predict the functional outcome after reorganisation?
3.6. Early compensation
3.6.1. How does the brain compensates the damage before symptoms appear?
3.6.1.1. http://www.ncbi.nlm.nih.gov/pubmed/19490021
3.6.1.1.1. "Our results suggest that PD subjects tap into motor reserve, increase the spatial extent of activation and demonstrate NAR to maintain near-normal motor output."
3.6.1.2. http://www.ncbi.nlm.nih.gov/pubmed/16814549
3.6.1.2.1. there is reorganisation of the corticomotor representation of the hand in PD, even at a relatively early stage of the disease, and suggest a dynamic process of reorganisation in the motor cortex due to an increase in the pallidal inhibitory inputs to the thalamo-cortical projections.
3.6.2. Do mutations in the genes with cause the genetic variants of PD affect the (motor) circuits in the brain of healthy mutan carriers?
3.6.2.1. Mapping preclinical compensation in Parkinson's disease: an imaging genomics approach. http://www.ncbi.nlm.nih.gov/pubmed/19877238
3.6.2.1.1. "In two separate experiments, Parkin mutation carriers displayed stronger activation of rostral supplementary motor area (SMA) and right dorsal premotor cortex (PMd) during a simple motor sequence task and anterior cingulate motor area and left rostral PMd during internal movement selection as opposed to externally cued movements. Because mutation carriers were not impaired at performing the task, the additional recruitment of motor cortical areas indicates a compensatory mechanism that effectively counteracts the nigrostriatal dysfunction"
3.6.3. Do environmental factors/toxins affect the (motor) circuits of healthy people in fMRI?
3.7. Does toxic induced PD in animals has the same compensation mechanisms?
3.8. What cases of cerebral reorganisation are described for different neurodegenerative diseases?
3.8.1. i.g. increase in creativity in patients with primary progressive aphasia http://www.ncbi.nlm.nih.gov/pubmed/18057074
4. How can cerebral reorganisation be influenced?
4.1. Can a neuroelectrophysiological technique (DBS,cortical magnetic stimulation) help with the cortical repair?
4.2. Can the removal of the pathogenic factor(Iron, Alpha-Sinuclein) increase the brain's chance to reorganisate.
4.3. can physical activity lead to structural and functional brain alterations in PD?
4.3.1. Physical exercise administrated in advance protect the animal's basal ganglia from MPTP toxicity
4.3.1.1. ? Does this happen because of the reorganisation of the frontal cortex especially the Anterior Cingulate Cortex?
5. What are the effects of reorganisation on the brain function?
5.1. Is it a maladaptive process?(like in cardiac insufficiency) Good on the short run but damaging on the long run?
5.1.1. Helmich Dissertation
5.1.1.1. It seems that it is not maladaptive but completely compensatory because patients with a benign clinical course seem to gather the biggest changes.
5.1.1.2. Although these connectivity changes may help retain cortico-‐striatal coupling in the face of (dorsolateral) striatal dysfunction, we hypothesized that they may also cause maladaptive changes at other levels of the network
5.1.1.2.1. For instance,the cortical area showing cortico-‐striatal remapping (parietal cortex) also showed reduced functional connectivity with other portions of the motor system (i.e.the motor cortex).
5.2. Does motor compensation lead to psychological damage(dementia) on the long-run or does it actually have a protective affect.
5.2.1. The Cognitive and Computational Neuroscience of Categorization, Novelty-Detection http://www.youtube.com/watch?v=2Ei6wFJ9kCc
5.2.2. It remains unclear whether the increased visual cortex activity observed during motor imagery in chapter 6 prevents behavioral impairments (making it an instance of compensatory reorganization) or whether it reflects less efficient cortical activation (making it an instance of pathological reorganization).
6. Methods we could use for our research
6.1. Use of fMRI,PET-scan and [F18]Dopamine imaging to see the new motor circuits.
6.2. Can it be evaluated by strict paraclinical methods?
6.3. using magnetic resonance spectroscopy (MRS, to measure N-‐acetyl aspartate (NAA) concentrations in the basal ganglia to study it's connectivity
7. How is the movement control influenced through the neurodegeneration/cerebral reorganisation
7.1. rhythm
7.1.1. thalamic/cortical influence?
7.1.2. http://www.ncbi.nlm.nih.gov/pubmed?term=freezing%20of%20gait%20rhythm%20control
7.1.2.1. These results suggest that a paradigm shift should take place in our view of freezing of gait. PD subjects with freezing of gait have a continuous gait disturbance: the ability to regulate the stride-to-stride variations in gait timing and maintain a stable walking rhythm is markedly impaired in subjects with freezing of gait. In addition, these findings suggest that the inability to control cadence might play an important role in this debilitating phenomenon and highlight the key role of dopamine-mediated pathways in the stride-to-stride regulation of walking.
7.1.3. http://www.ncbi.nlm.nih.gov/pubmed/9810954
7.1.3.1. These results suggest that pallidal activity can correlate inversely with the severity of dystonia, perhaps due to activity dependent changes in neuronal function resulting from repeated voluntary movement.
7.2. emotion
7.3. visual control
7.4. can certain movements be improved by cerebral reorganisation?
7.5. how can the freezing of gait be influenced?
7.5.1. http://www.ncbi.nlm.nih.gov/pubmed/18668619
7.5.1.1. "Overall, the findings suggest a smaller capacity for compensation in patients suffering from FOG. Especially when attention is overloaded, the therapeutic window and the practical applicability of cueing seem more limited."
7.6. somatosensory input diminuished
7.6.1. Helmich Dissertation
7.6.1.1. This suggests that the cortico-‐striatal circuit plays a central role in altered somatosensory processing in PD, although it should be kept in mind that these changes may be multi-‐synaptic. ltered thalamic gating of afferent signals to the somatosensory cortex
7.7. motor compensation
7.7.1. PD patient cyclinghttp://www.youtube.com/watch?v=aaY3gz5tJSk
7.7.1.1. paper Snijders, AH: http://www.ncbi.nlm.nih.gov/pubmed/21462254, http://www.ncbi.nlm.nih.gov/pubmed/20357278 In the video accompanying this article, we present another patient with a similarly preserved ability to ride a bicycle, despite marked FOG. It concerns a 57-year- old man who had been treated with bilateral subtha- lamic nucleus stimulation for severe motor fluctuations, 12 years after onset of PD. The home video shows the patient’s severe gait disorder, mainly caused by FOG. However, he can immediately generate smooth cycling
7.7.1.1.1. Why is bicycling preserved in some patients with freezing of the gait?
7.7.1.1.2. Research ideas about preserved cycling/preserved movements in general in PD Patients
7.7.2. Bas Bloem TEDx http://www.youtube.com/watch?v=jaAXuiCP18Q
7.7.3. Michael J Fox http://www.youtube.com/watch?v=ECkPVTZlfP8&feature=related
7.7.4. de novonmotor skill learning in non-demented PD patients still preserved:http://www.ncbi.nlm.nih.gov/pubmed/21760898
7.8. Cueing
7.8.1. tactile
7.8.2. visual
7.8.3. auditive
7.8.4. fMRI Imaging of cueing?