2. CAPÍTULO II: MARCO REFERENCIAL
2.4. Marco Contextual
2.4.1. La Universidad Distrital y su contexto histórico
We then investigated the behavioral relevance of organized intrinsic brain activity. Specifically, we explored whether variations in sensory experiences relate to altered patterns of intrinsic brain activity in the resting state, beyond the immediate experience. First, we tested short-‐term modulation of ICN activity by exposing healthy subjects to repeated painful stimulation across 11 consecutive days59. In a different study we explored long-‐term differences in organized intrinsic brain activity. We tested whether aberrant visual perception of synesthetes, healthy subjects that consistently perceive unimodal stimuli (grey letters) as multimodal stimuli (grey letters as colored letters; letters associated with tones) is related to permanent changes in the intrinsic brain architecture (Dovern et al, J Neurosci, under revision).
INTRINSIC FUNCTIONAL BRAIN NETWORKS IN HEALTH AND DISEASE Valentin Riedl, 2012
In the study on short-‐term plasticity of intrinsic brain activity we exposed healthy subjects to identical painful stimuli on 11 consecutive days and explored intrinsic FC in ICNs during rest before (preREST) and after (postREST) stimulation. On a network level, we found that repeated pain selectively increased FC in the sensorimotor ICN (SMN) during postREST. We also found that the degree of increased FC during postREST correlated with the subjective experience of pain intensity the subjects had during stimulation. After 11 days, FC of the ventromedial prefrontal cortex (vmPFC) in the SMN even predicted the intensity a subject will perceive during the final, forthcoming
stimulation. This study revealed experimentally induced plasticity of organized intrinsic brain activity in response to repeated pain.
These results on modulated intrinsic brain activity with repeated pain are in line with task-‐fMRI studies testing acute pain processing. While somatosensory cortices process sensory discriminatory information of a pain sensation, the vmPFC has been ascribed a modulatory role in pain perception69-‐71. Hence, our data show that repeated pain selectively alters intrinsic connectivity between brain regions initially involved in processing acute pain sensations.
“Chronic pain is a state of continuous learning”72. In our study, predictive coding in the vmPFC only evolved after subjects had repeatedly experienced, or learned, this
particular situation. The anticipatory role of the vmPFC in the resting state might account for this learning effect. The literature on pain processing shows opposite directions of prefrontal activity between healthy subjects and patients suffering from chronic pain70,71,73. Healthy subjects that habituate to repeated pain show decreased activation in prefrontal cortex during pain processing71. In chronic pain patients, however, vmPFC is the only region within the pain network being more strongly involved in pain processing as compared to normal subjects70. Our data imply that a
INTRINSIC FUNCTIONAL BRAIN NETWORKS IN HEALTH AND DISEASE Valentin Riedl, 2012
75
In the following, I will relate the changes of intrinsic brain activity we found in response to pain to similar changes observed in other sensory and cognitive modalities.
Robertson et al showed that learning of a difficult spatial navigation task across several minutes changes FC in the resting state immediately after the task57. These changes selectively occurred in an ICN supposed to process attention to spatial information. In a different study, subjects had to detect a visual target on a screen and learned this task for several hours60. Again, the FC of primary visual and attention related brain regions increased from the resting state before learning the task to the resting state after successful performance of the task. Together, these and our data show that configurations of intrinsic brain activity change with the repeated experience or performance of somatosensory, visual and motor tasks. This suggests that ICNs of certain functional entities are integrated into a stable architecture of intrinsic brain activity, and are selectively modulated by recent experiences or different cognitive states. A possible interpretation of these data is that intrinsic brain activity might be involved in memory coding of past experiences and continuously adapts with learning. Two recent studies explored the FC of the hippocampus as an integrator of new
memories with the cortex after learning tasks. Both studies showed that coherent brain activity between hippocampi and cortex was increased in the resting state after a memory task74 and this FC correlated with later memory retrieval75.
In addition to above described short-‐term modulations of intrinsic brain activity, we also investigated state dependent differences in the intrinsic functional architecture. Individuals with synaesthesia are healthy subjects with altered sensory experiences since birth76. They report additional color perceptions while viewing numbers or letters. These additional experiences are stable across years (e.g. an “a” always occurs in light blue) and are hypothesized to relate to hyperconnectivity between visual grapheme, color and multimodal integration sites in the cortex77,78. We therefore investigated organized intrinsic brain activity in ICNs covering primary sensory and integration sites in subjects with synaesthesia and controls (Dovern et al, J Neurosci, under revision). We found both a global and a specific (visual to fronto-‐parietal networks) increase of FC in grapheme-‐color synaesthesia. Moreover, this increased intrinsic network connectivity reflected the strength of synaesthetic experiences. This is the first study to investigate organized intrinsic brain activity in synaesthetes and also first evidence for increased functional hyperconnectivity in synaesthesia.
INTRINSIC FUNCTIONAL BRAIN NETWORKS IN HEALTH AND DISEASE Valentin Riedl, 2012
Beyond a better understanding of the neural mechanisms of synaesthesia, our results fit into recent approaches investigating influences of inherited or acquired variations of intrinsic brain circuits on human behavior like feeling, experiences, and action patterns. The question is if organized intrinsic brain activity is linked to emotional and cognitive functions. Seeley and colleagues showed that FC in a salience related ICN (SN)
comprising anterior cingulate cortex and bilateral insula correlated with the level of anxiety measured in prescan resting state before the fMRI session61. In another study, Hampson et al. showed that the strength of FC in the default mode network (DMN) correlated with performance on a working memory task, during the task and also during postTASK resting state79. A very recent study also showed correlations between FC measures and personality traits80. In combination, our data suggest that differences in intrinsic network connectivity are directly related to the phenomenology of human experiences and continuously change with further experiences.