Cortisol plasticity Flashcards
Intro
• Dorsal column-medial lemniscal pathway – ascending
o Major route by which touch and proprioceptive information ascend to cerebral cortex
o Primary somatosensory cortex thalamus (VP nucleus) medulla (med lemniscus dorsal column nuclei) dorsal column in SC via large dorsal root axons
• Spinothalamic pathway
o Major route by which pain and temperature information ascend to CC
o Primary somatosensory cortex thalamus (intralaminar and VP nuclei) medulla spinothalamic tract dorsal column in SC via small dorsal root axons
• Somatic sensory areas of cortex – areas lie in peripheral lobe
o Central sulcus
o SC (area 1 (post-central gyrus – tactile discrimination), 2 (size/shape recognition), 3a (proprioception), 3b (touch))
o Posterior parietal cortex (areas 5, 7)
Merzenich overview
• Cajal – belief with brain injury = no possible solutions
• Changed due to Merzenich experiment set in 1980’s – based on idea the brain can change
• Single-unit recordings in SC used to map receptive field
• Used owl monkyes – similar brain to humans (same lobes and functional areas, relative areas) – big difference = convolusions (more sulci, ridges and valleys – increased SA for neurons in brain)
• Implanted electrodes in SS cortex in postcentral gyrus – recording electrodes from sensory corticol neurons to get them to fire = poke pressure (can do different – stroking, pain, heat etc.) in receptive field in arm (neurone firing changes depending on where pressure applied)
• Mapped out areas of brain
o Similar – legs into deep central sulcus
o Digits good representation in SS cortex
o Make corticol representation maps depending on where responding with pressure
Merzenich 1984
- Middle finger chopped off in monkey – 6w later mapping again = neurons in brain are still viable and have changed their representation from 3 to fingers 2 and 4 (encroached on areas) conclusive evidence for plasticity in brain
- Ethical issues with cutting off finger
Merzenich 1991
1991 Merzenich
• Post-injury a few weeks sutures undone and re-map
• Medial aspect of 3 and 4 – neurons have merged together (no border) – neurons responding to both fingers (change in corticol representation)
• Can you train this?
• Cylinder = raised letters like braille (trained monkeys to spin cylinder on stick – feeling letters as they go by) – maps out fingers (particular focus on ends of fingers – more corticol neurons respond to these post-training)
• Can change SSC as a result of training
Sanes and Donoghue 1990
- Rat barrel cortex experiments – have whiskers, at night they don’t have good eyesight so rely on whiskers (vibrissae) and smell – similar to Merzenich first experiment (BC associated with 7th nerve) (see brain representation on SSC for each whisker – in layer of 4 SSC – each whisker has a numbered area)
- First experiment (1990) – cut nerve (normal somatotopic arrangement transected areas which subserve whiskers respond to forelimb and periocular) – subsequent papers = cut whiskers off (experiments work well in owl monkeys and rats but what about humans?)
Sanes 1989
- Accompanying paper demonstrated map of MC (MI) output was recognized when examined 1w-4m after MN lesion in adult rats – measured extent of functional reorganization that occurs within first hours after the lesion
- Shifts in MI output tested by stimulation at MI vibrissa site pre and post 10 hours after nerve section of branches of facial nerve
- Post-transection (no movement of forelimb EMG activity was evoked by intracorticol electrical stim within vibrissa (within hours of transection, stim elicited forelimb EMG responses that were comparable to those obtained by stim within pre-transection forelimb area
- Re-mapping of MI after nerve transection indicated forelimb boundary has shifted about 1mm medially from original location into former vibrissa territory (10 hours)
Ramachandran 1992
• What happens when things go wrong? – phantom limb pain (driving nails into palm of hand)
• Many amputees – noted phenomenon where people feel missing fingers in shoulder and face – use cotton swab to map out digits on face and shoulders
• Seems to be associated with traumatic amputations not surgical – unknown cause
• 1998 – what is occurring in brain? – Topographical reorganisation
o PET scanner and amputees – mapped areas with colours
o On amp side see no green as no hand – but face and arm merged together not same spread as good side – PL comes from maladaptice plasticity in brain (not good) corticol neurons changed function = pain
• Mirror therapy (trick brain into thinking limb is there)
o Mirror down mid-line of body – look from one side and put both hands (amputated hand moving appears as amputated limb moving)
o Trick brain into thinking limb is there, and it works very well (high impact therapy) – believed Ramachandran experiments – face and upper arm neuronal areas separated (physiology evidence-based therapy via clinical efficacy)
Weeks 2000
- PET to measure regional CBF in sighted and congentially blind subjects performing auditory localization tasks – during scanning, spectral and binaural cues of localized sound were reproduced by sound system and headphones
- During tasks that required auditory localization both sighted and blind strongly activated post parietal areas – blind also activate association areas in right occipital cortex (foci similar to areas identified in visual location and motion detection experiments in sighted)
- Blind demonstrated visual to auditory cross-modal plasticity with auditory localization activating association areas originally intended for dorsal-stream visual processing
Buchel 1998
- Congenitally blind = feel braille letters and visual cortex lights up due to sensory finger feedback (more neurons and power in congenital)
- Use event-related fMRI to characterize neuronal responses mediating aversive trace conditioning – neural auditory tones paired with aversive sound (unconditioned stim) and conditioned
- Diff responses (CS+ and CS-) related to conditioning, observed in anterior cingulate and anterior insula, regions previously implicated in delay fear condition – diff responses in amygdala and hippo that were best characterized with time x stimulus interaction (rapid adaptation of CS+ specific responses in medial temporal love)
- Activation of anterior hippo in experiment supports view that its role in trace conditioning is to maintain a memory trace between offset of CS+ and delayed onset of US to enable associative learning in trace conditioning
Finney 2001
- Investigate similar cross-modal plasticity occurs in auditory cortex – use fMRI to measure visually evoked activity in auditory areas of early-defeaned and hearing individuals
- Deaf = activation in a region of right auditory cortex (Brodmann’s areas 42 and 22, as well as 41 (primary auditory cortex)) – early deafness results in processing of visual stim in auditory cortex
Merabet and Pascual-Leone 2010
- Nature review summary
- Crossmodal changes following blindness (recruitment of occipital visual cortex) – braille reading and tactile discrimination, auditory localization and discrimination, verbal memory and language
- CM changes following deafness (recruitment of auditory cortex) – sign language, visual tasks, vibro-tactile stimulation
Karni 1995
- Non-piano players and trained them in sequence of finger movements (do sequence and train this many times per day = becomes second nature)
- fMRI of local blood oxygenation level-dependent (BOLD) signals evoked in PMC (M1) – pre-training a comparable extent of M1 was activated by both sequences
- Habituation – repeating a sequence within a brief time window initially resulted in a smaller area of activation
- Enhancement – but later in larger area of activation – suggesting a switch in M1 processing mode within the first session (fast learning)
- Week 4 training – concurrent with asymptomatic performance, the extent of cortex activated by practiced sequence enlarged compared with unpracticed, irrespective of order (slow learning)
- Changes persisted for several months – results suggest a slowly evolving, long-term, experience-dependent reorganization of adult M1, may underlie acquisition and retention of motor skill
Barsi 2008
• Measure peak to peak mag = number at particular intensity (stimulus/response curves) – MEP mag v stim intensity = sigmoidal curve
• Compared effects of 3 paradigms on cortical excitability in healthy subjects – cortical ex from flexor muscles of fingers – 20-minute therapy sessions of:
o 1. FES of finger flex and ex
o 2. Vol movement with sensory stim
o 3. Therapeutic FES where stim augmented vol activation
• TFES training = sig increase in MEP mag throughout stim range, suggesting an increase in cortical ex (neither FES nor vol movement had such an effect)
• Combination of vol effort and FES has greater potential to induce plasticity in MC and TFES might be a more effective approach in rehab after stroke then FES or repetitive vol training alone
Pascual-Leone 2005
• Normal subjects taught to perform with one hand a 5 finger exercise on keyboard to musical interface – instructed to perform fluently without pauses and without skipping a key, paying attention to keeping interval and duration between each key press the same (subjects studied on 5 days, each day they had a 20hour practice session followed by a test – test was 20 reps of 5 finger exercises and number of sequence errors counted
• Error numbers decreased, and duration, accuracy and variability of intervals between key pushes improved sig over 5 days – before first practice TMS, and daily thereafter, focused TMS to map motor cortical areas targeting long finger flex and ex muscles bilaterally, as perf improved TMS threshold decreased for both muscle groups (but size of cortical rep increased sig with 20-30min rest period after practice and test session)
• Mental practice = similar reogranisation of motor output of one observed in groupd of subjects that physically practiced the movements (mental practice alone may be sufficient to promote plastic modulation of neural circuits placing subjects at an advantage for faster skill learning with min phys practice, by making reinforcement of existing connections easier and maybe speeding up sprouting and memory consolidation
• Big change in cortical spinal ex - due to Friday practice session or due to practice between Monday and Friday? – Group 1 (continued daily practice) group 2 (stopped) – 4 week follow up muscle maps were obtained on Mondays (before first practice session for group 1) and Fridays (after last practice session for group 1)
o 1 = improved cortical output maps on Friday showed peak and decrease in size despite continued perf improvement – oppositely maps obtained Monday pre-practice and following weekend rest showed small change from baseline with a tendency to increase in size over the study
• Flexible, short-term modulation of existing pathways represent a first and necessary step leading up to longer-term structural changes in intra-cortical and subcortical networks as skills become overlearned and auto
Lunbye-Jensen 2005
- Vol movement patient aims to follow blue screen – changes in cort ex induced by 4 weeks of heavy strength training or visuomotor skill learning investigated (inpu-output measurments for biceps brachii MEP’s elicited by TMS were obtained at rest and during vol contraction in course of training – training paradigms induced specific changes in motor performance capacity of the subjects
- Strength training group increased max dynamic and isometric muscle strength 31% and 12.5%
- Skill learning group improved skill perf significantly
- One training bout only sig change in TMS parameters was an increase in skill learning group maximal MEP at rest for subjects performing skill training
- Repeated skill training 3/week for 4w sig increased at rest and during contraction
- MEPmax and slope of in-out relation both decreased sig at rest but not during contraction in strength-trained subjects
- Significant correlation between changes in neurophys parameters and motor perf was observed for skill learning but not strength training (increased corticospinal ex may develop over several weeks of skill training and indicate changes may be of importance for task acquisition
- THM – only see changes in ex in voluntary, active, challenging and engaging motor task (rep TMS plagued by individual variability – who does this work in/not and why?
