Limits...
Genetic subtype differences in neural circuitry of food motivation in Prader-Willi syndrome.

Holsen LM, Zarcone JR, Chambers R, Butler MG, Bittel DC, Brooks WM, Thompson TI, Savage CR - Int J Obes (Lond) (2008)

Bottom Line: Both PWS subgroups showed greater activity in response to food pre- and post-meal compared with the healthy-weight group.These preliminary findings are the first functional neuroimaging findings to support divergent neural mechanisms associated with behavioral phenotypes in genetic subtypes of PWS.Results are discussed within the framework of genetic mechanisms such as haploinsufficiency and gene dosage effects and their differential influence on deletion and UPD subtypes, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA. lholsen@partners.org

ABSTRACT

Background: Differences in behavioral phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) (chromosome 15q deletions and maternal uniparental disomy 15 (UPD) indicate that distinct neural networks may be affected. Though both subtypes display hyperphagia, the deletion subgroup shows reduced behavioral inhibition around food, whereas those with UPD are generally more able to maintain cognitive control over food intake impulses.

Objective: To examine the neural basis of phenotypic differences to better understand relationships between genetic subtypes and behavioral outcomes. We predicted greater food motivation circuitry activity in the deletion subtype and greater activity in higher order cognitive regions in the UPD group, especially after eating.

Design and participants: Nine individuals with PWS due to UPD and nine individuals with PWS due to (type 2) deletion, matched for age, gender and body mass index, underwent functional magnetic resonance imaging (fMRI) while viewing food images during two food motivation states: one before (pre-meal) and one after (post-meal) eating a standardized 500 kcal meal.

Results: Both PWS subgroups showed greater activity in response to food pre- and post-meal compared with the healthy-weight group. Compared with UPD, the deletion subtype showed increased food motivation network activation both pre- and post-meal, especially in the medial prefrontal cortex (mPFC) and amygdala. In contrast, the UPD group showed greater activation than the deletion subtype post-meal in the dorsolateral prefrontal cortex (DLPFC) and parahippocampal gyrus (PHG).

Conclusion: These preliminary findings are the first functional neuroimaging findings to support divergent neural mechanisms associated with behavioral phenotypes in genetic subtypes of PWS. Results are discussed within the framework of genetic mechanisms such as haploinsufficiency and gene dosage effects and their differential influence on deletion and UPD subtypes, respectively.

Show MeSH

Related in: MedlinePlus

Genetic subtype comparison of the food > baseline contrast in the Pre-Meal condition. Regions demonstrating greater activation in the DEL group compared to the UPD group are shown in orange and include the bilateral DLPFC, right insula, right fusiform gyrus, and bilateral premotor and motor cortex. UPD > DEL regions in the food>baseline contrast are shown in blue and include the posterior cingulate gyrus and left MTG.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2643328&req=5

Figure 1: Genetic subtype comparison of the food > baseline contrast in the Pre-Meal condition. Regions demonstrating greater activation in the DEL group compared to the UPD group are shown in orange and include the bilateral DLPFC, right insula, right fusiform gyrus, and bilateral premotor and motor cortex. UPD > DEL regions in the food>baseline contrast are shown in blue and include the posterior cingulate gyrus and left MTG.

Mentions: The main contrasts of interest for this investigation centered on directly comparing PWS genetic subtypes in their neural response to food images before and after eating. For the pre-meal contrast, individuals in the DEL group exhibited greater activation than the UPD group in the a priori ROIs of the amygdala, mPFC, insula, hippocampus, and PHG, as well as in several frontal regions, including the IFG, MFG, SFG, PreC, PostC, and in the MTG, TTG, STG, SMG, and caudate (see Table 2 and Figure 1). The UPD group showed a stronger BOLD response to food images pre-meal compared to the DEL group in the PHG and FG, in the MFG and CING, and in several temporal lobe and posterior regions, including the ITG, SPL, angular gyrus, paracentral lobule, precuneus, and middle OG.


Genetic subtype differences in neural circuitry of food motivation in Prader-Willi syndrome.

Holsen LM, Zarcone JR, Chambers R, Butler MG, Bittel DC, Brooks WM, Thompson TI, Savage CR - Int J Obes (Lond) (2008)

Genetic subtype comparison of the food > baseline contrast in the Pre-Meal condition. Regions demonstrating greater activation in the DEL group compared to the UPD group are shown in orange and include the bilateral DLPFC, right insula, right fusiform gyrus, and bilateral premotor and motor cortex. UPD > DEL regions in the food>baseline contrast are shown in blue and include the posterior cingulate gyrus and left MTG.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2643328&req=5

Figure 1: Genetic subtype comparison of the food > baseline contrast in the Pre-Meal condition. Regions demonstrating greater activation in the DEL group compared to the UPD group are shown in orange and include the bilateral DLPFC, right insula, right fusiform gyrus, and bilateral premotor and motor cortex. UPD > DEL regions in the food>baseline contrast are shown in blue and include the posterior cingulate gyrus and left MTG.
Mentions: The main contrasts of interest for this investigation centered on directly comparing PWS genetic subtypes in their neural response to food images before and after eating. For the pre-meal contrast, individuals in the DEL group exhibited greater activation than the UPD group in the a priori ROIs of the amygdala, mPFC, insula, hippocampus, and PHG, as well as in several frontal regions, including the IFG, MFG, SFG, PreC, PostC, and in the MTG, TTG, STG, SMG, and caudate (see Table 2 and Figure 1). The UPD group showed a stronger BOLD response to food images pre-meal compared to the DEL group in the PHG and FG, in the MFG and CING, and in several temporal lobe and posterior regions, including the ITG, SPL, angular gyrus, paracentral lobule, precuneus, and middle OG.

Bottom Line: Both PWS subgroups showed greater activity in response to food pre- and post-meal compared with the healthy-weight group.These preliminary findings are the first functional neuroimaging findings to support divergent neural mechanisms associated with behavioral phenotypes in genetic subtypes of PWS.Results are discussed within the framework of genetic mechanisms such as haploinsufficiency and gene dosage effects and their differential influence on deletion and UPD subtypes, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA. lholsen@partners.org

ABSTRACT

Background: Differences in behavioral phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) (chromosome 15q deletions and maternal uniparental disomy 15 (UPD) indicate that distinct neural networks may be affected. Though both subtypes display hyperphagia, the deletion subgroup shows reduced behavioral inhibition around food, whereas those with UPD are generally more able to maintain cognitive control over food intake impulses.

Objective: To examine the neural basis of phenotypic differences to better understand relationships between genetic subtypes and behavioral outcomes. We predicted greater food motivation circuitry activity in the deletion subtype and greater activity in higher order cognitive regions in the UPD group, especially after eating.

Design and participants: Nine individuals with PWS due to UPD and nine individuals with PWS due to (type 2) deletion, matched for age, gender and body mass index, underwent functional magnetic resonance imaging (fMRI) while viewing food images during two food motivation states: one before (pre-meal) and one after (post-meal) eating a standardized 500 kcal meal.

Results: Both PWS subgroups showed greater activity in response to food pre- and post-meal compared with the healthy-weight group. Compared with UPD, the deletion subtype showed increased food motivation network activation both pre- and post-meal, especially in the medial prefrontal cortex (mPFC) and amygdala. In contrast, the UPD group showed greater activation than the deletion subtype post-meal in the dorsolateral prefrontal cortex (DLPFC) and parahippocampal gyrus (PHG).

Conclusion: These preliminary findings are the first functional neuroimaging findings to support divergent neural mechanisms associated with behavioral phenotypes in genetic subtypes of PWS. Results are discussed within the framework of genetic mechanisms such as haploinsufficiency and gene dosage effects and their differential influence on deletion and UPD subtypes, respectively.

Show MeSH
Related in: MedlinePlus