O que "ativação" cerebral em fMRI?

Como sempre, não deixe de ler ou dar uma olhada no original - não costumo reproduzir figuras originais nem colocar todos os links indicados nos textos de minhas traduções para não atravancar, porque muitos são (links) da Wikipedia, de artigos indisponíveis para simples mortais que não dispõem da senha, etc. Também reitero aqui: sempre leia os comentários, porque se alguns são mongos, muitos são informativos e acrescentam outras fontes de dados, além de fomentar discussões interessantes.

Neuroskeptic
Tuesday, 18 October 2011
What Is Brain "Activation" on fMRI?
Functional MRI is one of the most popular ways of measuring human brain activity. But what is "activity"?

Fundamentalmente, a atividade neural consiste em potenciais elétricos e sinais químicos. A fMRI não os mede diretamente. Ao invés, ela mede modificações no conteúdo de oxigênio no sangue de diferentes partes do cérebro.

Quanto mais os neurônios disparam, mais oxigênio estão consumindo, ainda que a oxigenação em verdade aumente como se fosse uma compensação para esta atividade, e este aumento é o que está sendo medido. As modificações de oxigenação associadas à ativação (ao disparo) neuronal é chamada de resposta BOLD.

Utilizando a fMRI, pode-se medir a BOLD e obter algumas blobs (manchas coloridas) da ativação (NT - veja ilustração no original). Mas o que significa quando uma região do cérebro é ativada? Assim como nenhum homem é uma ilha, nenhuma região cerebral pode fazer qualquer coisa sozinha. Toda área recebe inputs de outras áreas, e também envia outputs.

Assim, se uma área parece estar mais ativa, isso pode significar uma de três coisas:

1. ela está enviando mais outputs
2. ela está recebendo mais inputs
3. ela está realizando mais processamento "interno" naquela área - "falando consigo mesma"

Qual delas contribui para a BOLD? Sabe-se que a (1) output da área em questão - não é uma das principais contribuições para o sinal de fMRI, mas e quanto à (2) e à (3)? Um estudo de 2010 (NT - ver link no original), que tive oportunidade de ler, argumenta que 80% do sinal BOLD são causados por processamento interno, e apenas 20% se devem ao input.
Eles tomaram alguns ratos e estimularam seus (dos ratos) bigodes. Utilizando eletrodos, mediram as mudanças de oxigenação sanguínea em uma área chamada de córtex "barrel" (NT - córtex de tubo?), que lida com sensações que têm os bigodes como base (em verdade não utilizaram fMRI, mas isto teria sido visto como um sinal BOLD se tivessem utilizado).

Mas então eles acrescentaram uma droga chamada muscimol ao córtex "barrel". O muscimol reduz a ativação neuronal, mas não afeta o input sináptico. Eles demonstraram que o muscimol reduziu muito a resposta de oxigenação sanguínea, em uns 80%. Isto sugere que 80% do sinal não eram causados diretamente pelo input sensorial ao córtex, e sim gerados no interior do córtex.

De muitas maneiras, isto não é surpreendente: seria estranho se o córtex apenas estivesse recolhendo sinais e nada fizesse com eles. Entretanto, é bom poder ligar um número a quanto de processamento intra-cortical contribui para o sinal de fMRI. Pelo menos, em ratos.

Harris S, Jones M, Zheng Y, & Berwick J (2010). Does neural input or processing play a greater role in the magnitude of neuroimaging signals? Frontiers in neuroenergetics, 2 PMID: 20740075

Ajuda um pouco ler também a postagem de 24 de maio de 2010 do Neuroskeptic,
fMRI In 1000 Words

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Tendo em mente as postagens do Neuroskeptic acima, como avaliar os dados apresentados por artigos como:

Brain activation for reading and listening comprehension: An fMRI study of modality effects and individual differences in language comprehension
Augusto Buchweitz, Robert A. Mason, Lêda M. B. Tomitch and Marcel Adam Just
Psychology & Neuroscience, 2009, 2, 2, 111 - 123
http://www.ccbi.cmu.edu/reprints/Buchweitz_PsychNeurosci-2009_Read-Listen-reprint.pdf

Abstract. The study compared the brain activation patterns associated with the comprehension of written and spoken Portuguese sentences. An fMRI study measured brain activity while participants read and listened to sentences about general world knowledge. Participants had to decide if the sentences were true or false. To mirror the transient nature of spoken sentences, visual input was presented in rapid serial visual presentation format. The results showed a common core of amodal left inferior frontal and middle temporal gyri activation, as well as modality specifi c brain activation associated with listening and reading comprehension. Reading comprehension was associated with more left-lateralized activation and with left inferior occipital cortex (including fusiform gyrus) activation. Listening comprehension was associated with extensive bilateral temporal cortex activation and more overall activation of the whole cortex. Results also showed individual differences in brain activation for reading comprehension. Readers with lower working memory capacity showed more activation of right-hemisphere areas (spillover of activation) and more activation in the prefrontal cortex, potentially associated with more demand placed on executive control processes. Readers with higher working memory capacity showed more activation in a frontal-posterior network of areas (left angular and precentral gyri, and right inferior frontal gyrus). The activation of this network may be associated with phonological rehearsal of linguistic information when reading text presented in rapid serial visual format. The study demonstrates the modality fingerprints for language comprehension and indicates how low- and high working memory capacity readers deal with reading text presented in serial format.

A new method for fMRI investigations of language: Defining ROIs functionally in individual subjects
Evelina Fedorenko, Po-Jang Hsieh, Alfonso Nieto-Castañón, Susan Whitfield-Gabrieli and Nancy Kanwisher 2010
McGovern Institute for Brain Research, MIT
http://web.mit.edu/bcs/nklab/media/pdfs/Fedorenko.et.al.lang.frois.pdf

Previous neuroimaging research has identified a number of brain regions sensitive to different aspects of linguistic processing, but precise functional characterization of these regions has proven challenging. We hypothesize that clearer functional specificity may emerge if candidate language-sensitive regions are identified functionally within each subject individually, a method that has revealed striking functional specificity in visual cortex but that has rarely been applied to neuroimaging studies of language. This method enables pooling of data from corresponding functional regions across subjects, rather than from corresponding locations in stereotaxic space (which may differ functionally because of the anatomical variability across subjects). However, it is far from obvious a priori that this method will work, as it requires that multiple stringent conditions be met. Specifically, candidate language-sensitive brain regions i) must be identifiable functionally within individual subjects in a short scan, ii) must be replicable within subjects and have clear correspondence across subjects, and iii) must manifest key signatures of language processing (e.g., a higher response to sentences than nonword strings, whether visual or auditory). We show here that this method does indeed work: we identify 13 candidate language-sensitive regions that meet these criteria, each present in at least 80 percent of subjects individually. The selectivity of these regions is stronger using our method than when standard group analyses are conducted on the same data, suggesting that the future application of this method may reveal clearer functional specificity than has been evident in prior neuroimaging research on language.

Abstract Grammatical Processing of Nouns and Verbs in Broca's Area: Evidence from fMRI
Ned T. Sahin Steven Pinker and Eric Halgren
Cortex, (2006) 42, 540-562
http://www.nedsahin.com/wp-content/files/sahin_pinker_halgren_fMRI_of_inflection.pdf

Abstract.The role of Broca’s area in grammatical computation is unclear, because syntactic processing is often confounded with working memory, articulation, or semantic selection. Morphological processing potentially circumvents these problems. Using event-related functional magnetic resonance imaging (fMRI), we had 18 subjects silently inflect words or read them verbatim. Subtracting the activity pattern for reading from that for inflection, which indexes processes involved in inflection (holding constant lexical processing and articulatory planning) highlighted left Brodmann area (BA) 44/45 (Broca’s area), BA 47, anterior insula, and medial supplementary motor area. Subtracting activity during zero inflection (the hawk; they walk) from that during overt inflection (the hawks; they walked), which highlights manipulation of phonological content, implicated subsets of the regions engaged by inflection as a whole. Subtracting activity during verbatim reading from activity during zero inflection (which highlights the manipulation of inflectional features) implicated distinct regions of BA 44, 47, and a premotor region (thereby tying these regions to grammatical features), but failed to implicate the insula or BA 45 (thereby tying these to articulation). These patterns were largely similar in nouns and verbs and in regular and irregular forms, suggesting these regions implement inflectional features cutting across word classes. Greater activity was observed for irregular than regular verbs in the anterior cingulate and supplementary motor area (SMA), possibly reflecting the blocking of regular or competing irregular candidates. The results confirm a role for Broca’s area in abstract grammatical processing, and are interpreted in terms of a network of regions in left prefrontal cortex (PFC) that are recruited for processing abstract morphosyntactic features and overt morphophonological content.

Não deixe de ver esse poster:
http://pinker.wjh.harvard.edu/research/2004_HBM_poster.pdf

Que é ref. a um "antepassado" do artigo da Cortex de 2006:

Abstract Grammatical Processing in Broca's Area: Convergent Evidence from fMRI and Intracranial Electrophysiology
Ned T. Sahin, Eric Halgren, Istvan Ulbert, Don Schomer, Julian Wu, Anders Dale and Steven Pinker
preprint 2004
http://pinker.wjh.harvard.edu/articles/papers/sahin_pinker.pdf

Mais um artigo:

The effect of lexical priming on sentence comprehension: An fMRI study
Sharlene D. Newman, Kristen Ratliff, Tara Muratore & Thomas Burns Jr.
Brain Research doi:10.1016/j.brainres.2009.06.027
http://www.indiana.edu/~cnilab/senprime.pdf