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Interpreting the effects of altered brain anatomical connectivity on fMRI functional connectivity: a role for computational neural modeling.

Horwitz B, Hwang C, Alstott J - Front Hum Neurosci (2013)

Bottom Line: Many of these simulation studies found that structural connectivity changes do not necessarily result in matching changes in functional/effective connectivity in the areas of structural modification.Often, it was observed that increases in functional/effective connectivity in the altered brain did not necessarily correspond to increases in the strength of the anatomical connection weights.These results suggest that this interpretation can be mistaken.

View Article: PubMed Central - PubMed

Affiliation: Brain Imaging and Modeling Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health Bethesda, MD, USA.

ABSTRACT
Recently, there have been a large number of studies using resting state fMRI to characterize abnormal brain connectivity in patients with a variety of neurological, psychiatric, and developmental disorders. However, interpreting what the differences in resting state fMRI functional connectivity (rsfMRI-FC) actually reflect in terms of the underlying neural pathology has proved to be elusive because of the complexity of brain anatomical connectivity. The same is the case for task-based fMRI studies. In the last few years, several groups have used large-scale neural modeling to help provide some insight into the relationship between brain anatomical connectivity and the corresponding patterns of fMRI-FC. In this paper we review several efforts at using large-scale neural modeling to investigate the relationship between structural connectivity and functional/effective connectivity to determine how alterations in structural connectivity are manifested in altered patterns of functional/effective connectivity. Because the alterations made in the anatomical connectivity between specific brain regions in the model are known in detail, one can use the results of these simulations to determine the corresponding alterations in rsfMRI-FC. Many of these simulation studies found that structural connectivity changes do not necessarily result in matching changes in functional/effective connectivity in the areas of structural modification. Often, it was observed that increases in functional/effective connectivity in the altered brain did not necessarily correspond to increases in the strength of the anatomical connection weights. Note that increases in rsfMRI-FC in patients have been interpreted in some cases as resulting from neural plasticity. These results suggest that this interpretation can be mistaken. The relevance of these simulation findings to the use of functional/effective fMRI connectivity as biomarkers for brain disorders is also discussed.

No MeSH data available.


Related in: MedlinePlus

Functional connectivity changes following simulated brain lesions (Alstott et al., 2009). Dorsal (middle) and left and right hemisphere views of significant changes between lesioned and normal groups in simulated resting state functional connectivity (all in the dorsal view; hemisphere specific in the lateral views) between 66 anatomical areas constructed from the 998 ROIs used by Alstott et al. Red (blue) lines indicate a decreased (increased) correlation for the lesioned brains. Center of the lesion site indicated by the green “+.” (A) Lesion in sensory cortex; (B) lesion in temporo-parietal junction. Slightly modified from Alstott et al. (2009); [(A) is from Supplementary. Figure 1A; (B) is from Figure 4B].
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Figure 3: Functional connectivity changes following simulated brain lesions (Alstott et al., 2009). Dorsal (middle) and left and right hemisphere views of significant changes between lesioned and normal groups in simulated resting state functional connectivity (all in the dorsal view; hemisphere specific in the lateral views) between 66 anatomical areas constructed from the 998 ROIs used by Alstott et al. Red (blue) lines indicate a decreased (increased) correlation for the lesioned brains. Center of the lesion site indicated by the green “+.” (A) Lesion in sensory cortex; (B) lesion in temporo-parietal junction. Slightly modified from Alstott et al. (2009); [(A) is from Supplementary. Figure 1A; (B) is from Figure 4B].

Mentions: Other simulation studies have examined the effects of focal lesions on rsfMRI-FC, including investigations that employed structural models based on macaque connectivity (Honey and Sporns, 2008) and those that used structural data from humans (Alstott et al., 2009). We will discuss the latter of these. The structural, neural, and hemodynamic models used by Alstott et al. (2009) were the same ones as those employed by Honey et al. (2009): a DSI data set from 5 healthy human participants (Hagmann et al., 2008), the neural model of Breakspear et al. (2003) and the Friston et al. balloon model (Friston et al., 2000). A number of important findings were reported, including one showing that lesions along the cortical midline, in the temporo-parietal junction and in frontal cortex resulted in large and widely distributed reductions in rsfMRI-FC; some of these alterations involved regions outside the lesion site. In contrast, lesions of sensory and motor regions produced functional connectivity changes that were more localized to the area of the lesion (see Figure 3).


Interpreting the effects of altered brain anatomical connectivity on fMRI functional connectivity: a role for computational neural modeling.

Horwitz B, Hwang C, Alstott J - Front Hum Neurosci (2013)

Functional connectivity changes following simulated brain lesions (Alstott et al., 2009). Dorsal (middle) and left and right hemisphere views of significant changes between lesioned and normal groups in simulated resting state functional connectivity (all in the dorsal view; hemisphere specific in the lateral views) between 66 anatomical areas constructed from the 998 ROIs used by Alstott et al. Red (blue) lines indicate a decreased (increased) correlation for the lesioned brains. Center of the lesion site indicated by the green “+.” (A) Lesion in sensory cortex; (B) lesion in temporo-parietal junction. Slightly modified from Alstott et al. (2009); [(A) is from Supplementary. Figure 1A; (B) is from Figure 4B].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3822330&req=5

Figure 3: Functional connectivity changes following simulated brain lesions (Alstott et al., 2009). Dorsal (middle) and left and right hemisphere views of significant changes between lesioned and normal groups in simulated resting state functional connectivity (all in the dorsal view; hemisphere specific in the lateral views) between 66 anatomical areas constructed from the 998 ROIs used by Alstott et al. Red (blue) lines indicate a decreased (increased) correlation for the lesioned brains. Center of the lesion site indicated by the green “+.” (A) Lesion in sensory cortex; (B) lesion in temporo-parietal junction. Slightly modified from Alstott et al. (2009); [(A) is from Supplementary. Figure 1A; (B) is from Figure 4B].
Mentions: Other simulation studies have examined the effects of focal lesions on rsfMRI-FC, including investigations that employed structural models based on macaque connectivity (Honey and Sporns, 2008) and those that used structural data from humans (Alstott et al., 2009). We will discuss the latter of these. The structural, neural, and hemodynamic models used by Alstott et al. (2009) were the same ones as those employed by Honey et al. (2009): a DSI data set from 5 healthy human participants (Hagmann et al., 2008), the neural model of Breakspear et al. (2003) and the Friston et al. balloon model (Friston et al., 2000). A number of important findings were reported, including one showing that lesions along the cortical midline, in the temporo-parietal junction and in frontal cortex resulted in large and widely distributed reductions in rsfMRI-FC; some of these alterations involved regions outside the lesion site. In contrast, lesions of sensory and motor regions produced functional connectivity changes that were more localized to the area of the lesion (see Figure 3).

Bottom Line: Many of these simulation studies found that structural connectivity changes do not necessarily result in matching changes in functional/effective connectivity in the areas of structural modification.Often, it was observed that increases in functional/effective connectivity in the altered brain did not necessarily correspond to increases in the strength of the anatomical connection weights.These results suggest that this interpretation can be mistaken.

View Article: PubMed Central - PubMed

Affiliation: Brain Imaging and Modeling Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health Bethesda, MD, USA.

ABSTRACT
Recently, there have been a large number of studies using resting state fMRI to characterize abnormal brain connectivity in patients with a variety of neurological, psychiatric, and developmental disorders. However, interpreting what the differences in resting state fMRI functional connectivity (rsfMRI-FC) actually reflect in terms of the underlying neural pathology has proved to be elusive because of the complexity of brain anatomical connectivity. The same is the case for task-based fMRI studies. In the last few years, several groups have used large-scale neural modeling to help provide some insight into the relationship between brain anatomical connectivity and the corresponding patterns of fMRI-FC. In this paper we review several efforts at using large-scale neural modeling to investigate the relationship between structural connectivity and functional/effective connectivity to determine how alterations in structural connectivity are manifested in altered patterns of functional/effective connectivity. Because the alterations made in the anatomical connectivity between specific brain regions in the model are known in detail, one can use the results of these simulations to determine the corresponding alterations in rsfMRI-FC. Many of these simulation studies found that structural connectivity changes do not necessarily result in matching changes in functional/effective connectivity in the areas of structural modification. Often, it was observed that increases in functional/effective connectivity in the altered brain did not necessarily correspond to increases in the strength of the anatomical connection weights. Note that increases in rsfMRI-FC in patients have been interpreted in some cases as resulting from neural plasticity. These results suggest that this interpretation can be mistaken. The relevance of these simulation findings to the use of functional/effective fMRI connectivity as biomarkers for brain disorders is also discussed.

No MeSH data available.


Related in: MedlinePlus