Monday, January 28, 2008

Semantics and Brain - Comment from Matt Lambon Ralph

The following is a "guest post" from Matt Lambon Ralph. Sounds like some cool stuff Matt. Thanks for the info! I'll respond in the "comments" box soon.


Thanks for your thoughts and queries about our recent study, utilising rTMS to probe the function of the anterior temporal lobe, particularly with regard to its role in semantic memory.

Of course our jumping off point with this line of investigation was the neuropsychological studies of semantic dementia (SD) that a number of groups, including our own, have conducted. While the exact interpretation of the SD patients is a topic of current debate (see other blog entries here, Alex Martin’s 2007 Annual Review of Psychology, Karalyn Patterson et al’s NRN paper), the simplest explanation is that damage to the ATL leads to a specific semantic impairment – by which I mean one that affects any task that requires or involves semantic memory (in reception and expressive, verbal and nonverbal domains) but not other aspects of language, perception, problem-solving, etc. The selective nature of their impairment is really striking clinically as well as in formal testing. However, given the debate about the location of damage in SD – we have embarked upon a series of rTMS studies to provide converging evidence for what the SD data seem to be indicating. To license direct comparisons we have, wherever possible, tried to utilise the same tasks and test materials that we use in SD patients but in normal participants (collecting both RT and accuracy).

A quick summary of our findings: 10 mins of 1Hz rTMS over the left temporal pole significantly slowed synonym judgement times, slowed naming at the subordinate level (“Dalmatian”) but did not affect two “control” tasks (number judgement and number naming tasks – each of which was harder than the respective semantic tasks in terms of baseline reaction times – in order to rule out any findings being due to general difficulty). Basic level naming also slowed numerically but this change was not statistically significant. This pattern of findings is pretty much what one would expect from an SD perspective – as noted above, they exhibit receptive difficulties (they are impaired on the same synonym task) and expressive impairments (they are profoundly anomic) but not other taxing, non-semantic tasks. Indeed they tend to be rather good at number judgements (involving quantity judgements).

Greg makes a couple of interesting points about the design of the study and expresses a craving for more information with regard to TMS effects on nonverbal semantic tasks. So here’s some more information that might just help:

1. Control task vs. control area: the most common form of control method in TMS studies is the “control site” method – i.e. stimulate a site of non-interest to ensure that same results do not following from any form of non-specific brain stimulation. This is quite useful if one is trying to demonstrate that a new specific region (e.g., one that is identified in an imaging study) is required in a task. For our study, however, the motivation and research question was a bit different to the standard one underpinning most rTMS experiments. Given the SD data – we were specifically interested in probing the function of the ATL itself in normal participants: i.e., if we stimulate the same region that is maximally damaged in SD does it produce the same neuropsychological pattern as the patient? If the ATL atrophy in SD is a “red herring” - i.e., is not responsible for their semantic impairment then stimulating this same region in normal participants would not be expected to have any semantic effects. (Of course we are interested in which other brain regions are, and are not involved in semantic cognition but that is another story.) Because we were interesting in how closely ATL rTMS would mimic SD, we adopted the less common “control task” method. The “logic” of this is not that dissimilar to the idea of subtractions in neuroimaging – find a pair or selection of tasks, matched for general levels of difficult, which differ in terms of the representations/process of interest. We alighted upon numbers because we know SD patients tend to be good at them and also we were able to fashion a task in which the RTs were slower than the semantic tasks. By picking number judgement and number naming as two control tasks we mirrored the receptive and expressive aspects of the two semantic tasks. By gradually building up the range of semantic and control tasks used across studies, we should be able to construct a rather comprehensive picture of which aspects of cognitive behaviour involve this region.

Of course, it is possible that some of you may not be that interested in mimicking SD data as we were and consequently would like to see a control site as well. I’m pleased to say, therefore, that we have applied the “belt-and-braces” approach to more recent experiments by including both types of control method as well as other types of control tasks – and the findings are unchanged: ATL rTMS slows semantic tasks but not number or visual matching tests, whereas stimulation to a non-ATL site does not affect any of these tasks.

2. As Greg rightly points out, the results from SD (e.g., Bozeat et al., 2000, Neuropsychologia) suggest that the ATL is the basis for amodal semantic representations. Accordingly, we would really expect to see slowing on nonverbal as well as verbal semantic tasks after ATL stimulation. He suggests using a task like the Pyramids and Palm Trees Test (in which semantic associative knowledge is probed either with picture or word materials), which we commonly use in patient testing. As it happens, this is exactly the study we have just completed – and the results are just as predicted: rTMS to the ATL slows this task in both its verbal and its picture-based versions, and to the same degree.

So by combining the data from our published study with these new results, we can mirror the combination of problems observed in SD – i.e., the ATL seems to be involved in expressive and receptive semantic tasks for verbal and nonverbal domains. This is, of course, consistent with the idea that this region develops amodal representations that combine with information in other modality-specific regions to support semantic processing (Rogers et al, 2004, Psych Review).

Matt LR

1 comment:

Greg Hickok said...

Ok, so you've nicely answered the concerns about a control stimulation site, as well as other types of control tasks. The effect seems to be secure. Here's some other questions, though, mostly wondering whether the effect can be enhanced by tweaking the stim protocol:

1. Is your stimulation target location still only 1cm from the tip of the temporal pole? This seemed to me very anterior. Why this location?

2. Relatedly, do you think you might get stronger effects if you stimulated farther back? My reading of the SD literature leads me to think that the critical region is more posterior.

3. How about bilateral stimulation? Is that feasible?