Thursday, April 24, 2008

Wise-guy on PET, Part 2

And why all other methods in cognitive neuroscience (with the parenthetical exception of intracranial EEG) are rubbish. From his April 15 talk at the 15th annual meeting of the Cognitive Neuroscience Society.

After our initial recap of the wit and wisdom of Prof. Richard Wise, we learned that:
  1. Modern tractography has taught us nothing new.1
  2. "Broca's area and Wernicke's area have expanded like Balkan states." [uh, wouldn't that similie imply fragmentation, not expansion?]
  3. We should "throw out most of the literature from stroke aphasia."
  4. fMRI studies of language have "fostered confusion, not understanding."
  5. Hickok & Poeppel "have a job for life."
Now it's time to highlight Wise's own work and to explain why he's persisted in running PET studies while the rest of the field2 abandoned that methodology long ago. But first, let's be a bit didactic.3

fMRI Advantages

  • doesn't need radioactive tracers
  • better spatial resolution (1-2 mm)
  • event-related designs
  • can intermix trial types

fMRI Disadvantages

  • noisy – bad for auditory studies (although sparse-sampling methods help)
  • too claustrophobic for some people
  • poor imaging of OFC and ATL (due to susceptibility artifact4, although distortion-correction methods are being developed)
  • motion artifact with speaking aloud (although many studies have overcome this)

PET Advantages
  • quiet – good for auditory studies
  • more open and “naturalistic”
  • no susceptibility artifact
  • speaking aloud not a worry

PET Disadvantages

  • radioactive tracers
  • worse spatial resolution (4-5 mm)
  • brain activity over a 40 sec period
  • stuck with blocked designs
OK, now on to the two PET papers under discussion. The first study compared implicit comprehension of spoken and written language (i.e., passive listening and reading, no task). The idea was to demonstrate the existence of amodal semantic areas in the ATL that are activated to both spoken and written narratives (when each are compared to their respective control conditions). The second study compared speech comprehension and speech production, and is riddled with confounds because it's very difficult to control the content of self-referential, spontaneous narratives produced in response to cues. [NOTE: coverage of these experiments in the talk was minimal, brief, and primarily limited to the results. Thus, I have augmented the discussion with my reading of the papers.]

(4a) Spitsyna et al. 2006.
The stimuli and contrasts in this experiment were as follows:
Intelligible spoken and written narratives were contrasted with unintelligible auditory (spectrally rotated speech) and visual (false font) stimuli matched closely to the narratives in terms of auditory and visual complexity. Thus, during data analyses, the contrasts of the intelligible with the modality-specific unintelligible conditions were intended to demonstrate processing of speech and written language beyond the cortical areas specialized for early auditory and visual processing.
The results of these contrasts? Prominent activations in the ATL for both speech vs. rotated speech and written text vs. false font (greater in the L hemisphere than in the R). Another large cluster of activity was located posteriorly, at the junction of the L temporal, occipital, and parietal (TOP) cortices.

Fig. 1 (Spitsyna et al. 2006). The results of analyses within wavelet space of two contrasts: speech with rotated speech, and written text with false font. The estimated effect sizes, both positive (red–yellow) and negative (blue) results, expressed as Z-scores without a cutoff threshold, are displayed on axial brain slices from ventral to dorsal. The strongest positive effect size for each contrast was observed within the left anterior temporal cortex (arrows).

In his talk, Wise noted the anterior and posterior temporal clusters of activation (illustrated in the schematic below).

Fig. 8 (Spitsyna et al., 2006). An anatomical summary of the results, overlaid on the lateral (top row) and ventral (bottom row) surfaces of the left cerebral hemisphere, showing the convergence of spoken and written language in the left STS (pink shading) and in posterior (the TOP junction) and anterior (lateral TP and anterior FG) cortex (red shading). The auditory streams of processing are shown in blue, and the visual streams are in yellow.

In discussing these findings the authors state:
This anatomical model contrasts sharply with those recently presented by Hickok and Poeppel (2004) and by Catani and ffytche (2005), which ascribe an exclusive role for posterior temporal or inferior parietal cortex in the access to verbal meaning.
In addition, there was little (if any) involvement of Broca's area, which conflicts with the results of most fMRI studies [but not, apparently, with a replication of this experiment performed by Wise's group, using sparse-sampling techniques]. Furthermore,
Although previous imaging studies investigating both spoken and written language processing and cross-modal priming study have demonstrated inferior frontal gyrus activation, these studies involved performance of explicit metalinguistic tasks. In contrast, the present study and previous PET studies of implicit language processing do not emphasize a role for the left inferior frontal gyrus in implicit language comprehension.
Or as Wise put it, the metalinguistic tasks are "party games, not spontaneous speech" (or implicit comprehension).

(4b) Awad et al. 2006.
I was going to discuss this paper as well, but the caveats the authors put forth in their own Methods section made me abandon all hope. For instance,
Intelligible speech was contrasted with its “matched” baseline condition of an unintelligible auditory stimulus (spectrally rotated speech)...

During separate scans, the subjects generated self-referential propositional speech in response to cues (e.g., “tell me what you did last weekend”). The prompts were different from those that had been used to elicit the speech that had been recorded for the speech comprehension scans.

. . .

...a potential confound is that personal narratives vary in the richness of episodic detail they contain. ... Because the subjects were naive to the prompts they were going to receive during the speech production scans, to prevent previous rehearsal of stories with loss of spontaneity, we had no control over this aspect of the study.

An additional confound relates to the observation that subjects whose attention is not held by perception of meaningful stimuli or by performance of an explicit task exhibit a reproducible pattern of activity in midline anterior (prefrontal) and posterior (retrosplenial and posterior cingulate) cortex and in bilateral temporoparietal cortex.
OK, enough of that.

To summarize the Wise-guy's final message, the role of ATL regions in semantic memory has been largely overlooked in experiments using neuropsychological and fMRI methodologies, but not in those using PET or intracranial EEG (the latter discussed by Eric Halgren - speaker #2 in the session - in his talk on "ELECTROPHYSIOLOGY OF SEMANTIC RESPONSES IN THE ATL").


1 We must consider the possibility that he might not actually believe some of these statements...

2 With the notable exception of those using radioligands such as [11C] raclopride for dopamine D2/D3 receptors and PIB (Pittsburgh Compound-B) for amyloid plaques in the brains of Alzheimer's patients.

3 Sources include links from the Athinoula A. Martinos Center for Biomedical Imaging explaining MRI and PET, a review paper (Otte & Halsband, 2006), and my own semantic memory.

4 Susceptibility artifact is the signal dropout/distortion that occurs with fMRI, which limits the images that can be obtained from the orbitofrontal cortex and the anterior temporal lobes. In fact, the first speaker in the session, Matthew Lambon Ralph, mentioned
new fMRI studies utilizing a correction for the field inhomogeneities that plague the inferior aspects of the ATL.

Main References

Awad M, Warren JE, Scott SK, Turkheimer FE, Wise RJ. (2007). A Common System for the Comprehension and Production of Narrative Speech. Journal of Neuroscience, 27(43), 11455-11464. DOI: 10.1523/JNEUROSCI.5257-06.2007

Humans devote much time to the exchange of memories within the context of shared general and personal semantic knowledge. Our hypothesis was that functional imaging in normal subjects would demonstrate the convergence of speech comprehension and production on high-order heteromodal and amodal cortical areas implicated in declarative memory functions. Activity independent of speech phase (that is, comprehension and production) was most evident in the left and right lateral anterior temporal cortex. Significant activity was also observed in the posterior cortex, ventral to the angular gyri. The left and right hippocampus and adjacent inferior temporal cortex were active during speech comprehension, compatible with mnemonic encoding of narrative information, but activity was significantly less during the overt memory retrieval associated with speech production. Therefore, although clinical studies suggest that hippocampal function is necessary for the retrieval as well as the encoding of memories, the former appears to depend on much less net synaptic activity. In contrast, the retrosplenial/posterior cingulate cortex and the parahippocampal area, which are closely associated anatomically with the hippocampus, were equally active during both speech comprehension and production. The results demonstrate why a severe and persistent inability both to understand and produce meaningful speech in the absence of an impairment to process linguistic forms is usually only observed after bilateral, and particularly anterior, destruction of the temporal lobes, and emphasize the importance of retrosplenial/posterior cingulate cortex, an area known to be affected early in the course of Alzheimer's disease, in the processing of memories during communication.

Spitsyna, G, Warren JE, Scott SK, Turkheimer FE, Wise RJ. (2006). Converging Language Streams in the Human Temporal Lobe. Journal of Neuroscience, 26(28), 7328-7336. DOI: 10.1523/JNEUROSCI.0559-06.2006

There is general agreement that, after initial processing in unimodal sensory cortex, the processing pathways for spoken and written language converge to access verbal meaning. However, the existing literature provides conflicting accounts of the cortical location of this convergence. Most aphasic stroke studies localize verbal comprehension to posterior temporal and inferior parietal cortex (Wernicke’s area), whereas evidence from focal cortical neurodegenerative syndromes instead implicates anterior temporal cortex. Previous functional imaging studies in normal subjects have failed to reconcile these opposing positions. Using a functional imaging paradigm in normal subjects that used spoken and written narratives and multiple baselines, we demonstrated common activation during implicit comprehension of spoken and written language in inferior and lateral regions of the left anterior temporal cortex and at the junction of temporal, occipital, and parietal cortex. These results indicate that verbal comprehension uses unimodal processing streams that converge in both anterior and posterior heteromodal cortical regions in the left temporal lobe.

Other Refs

Catani M, ffytche DH. (2005). The rises and falls of disconnection syndromes. Brain 128:2224-39.

Hickok G, Poeppel D. (2004). Dorsal and ventral streams: a framework for understanding aspects of the functional anatomy of language. Cognition 92:67–99.

Otte A, Halsband U. (2006). Brain imaging tools in neurosciences. J Physiol Paris 99:281-92.

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At May 15, 2008 3:33 AM, Anonymous Anonymous said...

oh dear, another case of cultural misunderstanding across the pond! Did you actually understand any of the points he was trying to make at CNS or did you just pick up on key words and fill in the rest for yourself!

At May 15, 2008 4:07 AM, Blogger The Neurocritic said...

Oh dear, cultural misunderstanding indeed! Which part of the blog's sarcasm did you not understand?

At June 15, 2008 10:01 AM, Anonymous Anonymous said...

go dad!

At June 15, 2008 3:29 PM, Blogger The Neurocritic said...

Happy Father's Day to Professor Wise!

At December 06, 2012 6:16 AM, Anonymous bored said...

Modern tractography has taught us nothing new
- Wise works with patients. He wants to make them better, modern tractography has not helped us do this. He is correct.

"Broca's area and Wernicke's area have expanded like Balkan states." [uh, wouldn't that similie imply fragmentation, not expansion?]- Clearly he is referring to the number of states not the political systems. Many people from the Balkans would reject the notion of fragmentation so be careful. The number has grown, as has the geographical description of the term to no longer refer to those regions only surrounding the Balkan mountains- a bit like Broca and Wernicke's area.

We should "throw out most of the literature from stroke aphasia."- clearly an ironic comment as he as produced much of it. Irony my dear friend.

fMRI studies of language have "fostered confusion, not understanding."- show me one honest neuroscientist who disagrees with this and I'll illustrate how their studies have just contributed to the confusion. Humility.

Hickok & Poeppel "have a job for life."- a compliment if ever I've heard one.


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