Tuesday, 31 March 2015

Cognition in Progressive MS - a hard nut to crack!

J Neurol Sci. 2015 Mar 3. pii: S0022-510X(15)00124-0. doi: 10.1016/j.jns.2015.02.044. [Epub ahead of print]

Orienting network dysfunction in progressive multiple sclerosis.

Ayache SS, Palm U, Chalah MA, Nguyen R, Farhat WH, Créange A, Lefaucheur JP.

Among patients with multiple sclerosis (MS), cognitive impairment affects up to 70% of the population . The most frequently impaired domains are memory, processing speed and attention. Three main attentional networks were described: the alerting network responsible for controlling vigilance and performance during tasks, the orienting network in charge of orientation to external stimuli, and the executive control network that deals with solving conflicts, detecting targets, and focal attention. The evaluation of these networks is possible by the means of the Attention Network Test (ANT). To our knowledge, this test has been studied in patients with relapsing–remitting MS (RRMS) but not in MS patients with progressive subtypes. We postulated that the increase in lesion load and cerebral atrophy throughout disease progression might have more impact on the attentional capacities in progressive MS.

Regarding ANT performance, MS patients were found slower (MRT: 816.84 ± 142.8 vs 683.5 ± 93.1; p = 0.0006), and less accurate (MA 94.2 ± 9.4 vs 97.7 ± 5.8; p = 0.002) than their healthy counterparts. Looking at the network effect, MS patients had a significant deficit in the orienting network (54.2 ± 55.5 vs. 24.9 ± 29.4; p = 0.047), but not in the alerting (24.0 ± 32.1 vs. 27.3 ± 26.5; p = 0.53) or the executive control (159.1 ± 74.9 vs. 134.5 ± 37.7; p = 0.23) networks.

You might ask what the heck is the orienting network?!! It would appear from this study that there is exclusive dysfunction of this domain in progressive MSers.

Orienting network, is the network that directs attention to a target stimulus - an example of this is having your attention drawn to someone new entering into the room (you may have wandered what triggers this, now you know!). 

This is not easy to achieve, and is the product of a distributed neural network - involving the frontal eye fields (located in the frontal lobe), superior parietal lobe and temporal-parietal junction (where knowledge and intelligence originate from), superior colliculus (helps to orient the head and eyes to all types of sensory stimuli) and the pulvinar (virtually non-existent in the rat) of the thalamus (important in visual attention and eye movements).

The key is the amount of invested effort in terms of brain power which is required to maintain this network, with a constant recruitment of mental resources for post-production executive monitoring (i.e. what the heck am I seeing?) and preparatory processes for on-going monitoring (i.e. for continued ogling!). Impaired memory, and in particular, processing speed probably has a significant impact on high-load tasks such as this.


  1. Sorry NDG, you'll have to re-explain this in really simple language. I didn't follow at all

    1. Your memory, performance and even intelligence can be affected by the level of attention you give to a task. If you zone out (remember the days of school just lapsing into space), then you loose that piece of information. Here they describe three ways in which attention is directed in the brain: 1) vigilance to things occurring around you, 2) orienting/focusing on matters of interest, and 3) voluntary control of what you perceive.

      Now in progressive MS the orienting network seems to be affected preferentially; this will affect the accuracy of your memory as you're not directing your sight to areas of interest. The pathway by which the brain preforms this task is quite vast (going from the front of the brain, to middle of the brain and in the brainstem) and likely to take a hit as more lesions increase.

      The question is whether performance at the orienting network can be improved upon (as this may indirectly improve cognition)? We probably cannot do anything about overall memory (as this relies on the total number of cells and neurones available) or the processing speed (as this relies on the connections/tracts); which are the other areas affected in MS

  2. Is it a fair assumption that initially the cognitive effects tend to be less on the progressive type?

    1. Not at all, as the article states the areas affected are memory, processing speed and attention. Unfortunately all three worsen over time. Now primary progressive MS are tricky to understand with confusing data on cognition published.

  3. Would the new biotin treatment if successful help to nullify and or slow this? As I assume it's a neuro degeneration effect?

  4. Docs what do you think about this study promoted by Vaccinex? http://www.virtual-strategy.com/2015/03/31/vaccinex-provides-update-its-vx152503-phase-1-clinical-trial-multiple-sclerosis-patients#axzz3W08Vq5B5


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