Table 2.
Studies reporting neural function in PWS at the macrostructural level.
| Study | Methods | Sample | Mai findings |
|---|---|---|---|
| Akefeldt et al. 1997 [40] | EEG: Auditory brainstem response. | 7 participants with PWS (6 males, 4–25 y) 7 control participants with intellectual disability (5 males, 5–26 y) |
Atypicalities of auditory brainstem response compared to control group and laboratory reference values. |
| Dimitropoulos & Schultz 2008 [41] | fMRI: response to high vs. low calorie food images. | 9 participants with PWS (3 males, 8–38 y) 10 IQ and BMI matched control participants (4 males, 19–29 y) |
Increased amygdala, hypothalamus, insula and OFC activity when fasted in response to images of high vs. low calorie foods. |
| Halit et al. 2008 [42] | EEG: face and gaze perception. | 8 adults with deletion subtype of PWS (20–53 y) 8 with UPD subtype of PWS (19–52 y) |
Behavioural performance impaired for both genotypes, but ERP showed increased impairment in the deletion group: N170 amplitude larger for averted vs. direct gaze and inverted vs. upright faces in UPD, but not deletion group. |
| Hinton et al. 2006 [43] | PET: pre- and post-meal (400 & 1200 kcal) response to food images. | 13 participants with PWS (22–42 y) | Increased activity in medial OFC, temporal cortex and PFC usually found not seen in PWS following meals when viewing food images. |
| Hinton et al. 2006 [44] | PET: response to high and low incentive food images. | 13 participants with PWS (22–42 y) | Increased activation of amygdala and medial OFC typically seen in response to high vs. low incentive foods not found. |
| Holsen et al. 2006 [45] | fMRI: pre- and post-meal (500 kcal) response to food images and control animal images | 9 participants with PWS (1 male, mean 14.7 y) 9 age matched typically-developing controls (3 males, mean 14.4 y) |
PWS group showed reduced activity when viewing food vs. animal images in medial PFC and OFC in pre-meal condition than control group and greater medial PFC, insula, parahippocampal gyrus and amygdala activity in post-meal condition. |
| Holsen et al. 2009 [46] | fMRI: pre- and post-meal (500 kcal) responses to food images and control animal images. | 9 participants with PWS deletion subtype (2 males; mean 24.4 y) 9 participants with PWS UPD subtype (3 males; mean 20.8 y) 9 healthy weight controls (3 males; mean 23.6 y) |
Both PWS subtypes showed atypical response in both pre- and post-meal conditions compared to control group. Deletion vs. UPD: greater activity in deletion group in frontal/limbic areas, especially medial PFC and amygdala, in both pre- and post-meal conditions; greater activity in dorsolateral PFC and parahippocampal gyrus in UPD group in post-meal condition only. |
| Holsen et al. 2012 [47] | fMRI: pre- and post-meal 500 kcal) responses to food images and control animal images. | 14 participants with PWS (2 males, mean 23.3 y) 14 BMI & age-matched control participants (5 males; mean 25.0 y) 15 healthy weight age-matched controls (6 males; mean 23.1 y) |
Pre-meal: increased activity when viewing food vs. non-food images in nucleus accumbens and amygdala in PWS than either control group control group, and lower in hypothalamus and hippocampus. Post-meal: increased activity in hypothalamus, amygdala and hippocampus in PWS than either control group, but higher dorsolateral PFC and OFC in obese group not seen in PWS or healthy weight control group. |
| Key & Dykens 2008 [48] | EEG: N1 & P3 ERP response to food images according to categorisation/discrimination of food composition and quality. | 9 participants with deletion subtype of PWS (2 males, mean 22.9 y) 8 participants with UPD subtype of PWS (3 males, mean 22.4 y) 9 age-matched control participants (4 males, mean 21.7 y) |
N1 ERP suggested deletion group early processing by categorising mainly according to quantity, whilst UPD did so by quality and suitability for consumption more similarly to the control group. Later P3 response showed deletion group could discriminate foods by combinational suitability, but this later processing response was greater than that seen in UPD. Later P3 motivational processing of food images not seen in control group. |
| Kim et al. 2006 [49] | Resting-state PET while fasted. | 16 children with PWS (9 males, mean 4.2 y) 7 typically-developing siblings/relatives (4 males, mean 4.0 y) |
PWS group showed decreased metabolism in right superior temporal gyrus and left verebellar vermis, and increased metabolism in right OFC, bilateral medial PFC, right inferior and left superior frontal cortex, bilateral ACC, right temporal pole and left uncus. |
| Klabunde et al. 2015 [50] | fMRI: sessions where participants engaged in skin picking compared to sessions where they did no. | 17 participants with PWS (11 males, mean 15.7 y) | 2 main clusters showing greater activation during skin picking: right ACC & right middle frontal gyrus; primary somatosensory cortex, left inferior parietal lobule, supplementary motor area, left middle frontal gyrus and right posterior insula. Self-injury trauma scale scores negatively correlated with right insula and left precentral gyrus activity. |
| Mantoulan et al. 2011 [24] | Resting-state PET | 9 PWS teenagers (6 males; 12.7–18.6y, mean 16.4 y) 9 typically developing young adults (6 males; mean 21.2 y) |
Hypoperfusion in PWS, most strongly in ACC and superior temporal regions, but also in right orbitofrontal gyrus and postcentral gyrus. Positive correlations between Child Behaviour Checklist (CBCL) scale scores and rCBF in ACC (activity, social, & attention scales), superior temporal gyrus (attention & social scales), and superior frontal gyrus (activity scale). Negative correlation between rCBF in ACC and CBCL depression scale score. |
| Miller et al. 2007 [51] | fMRI: response to food images following glucose load. | 8 participants with PWS (6 males, mean 25 y) 8 typically-developing siblings (4 males, mean 27 y) |
Significantly increased activity ventromedial PFC in PWS group when viewing food images following glucose load. |
| Ogura et al. 2013 [52] | Resting state PET | 12 participants with PWS (6 males, 19–31 y) 13 age- & gender-matched controls (6 males, 19–29 y) |
Decrease metabolism in PWs group in the lingual gyri, cerebellum, right thalamus and left insula. Increased metabolism in bilateral angular and inferior frontal gyri and left middle frontal gyrus. Negative correlation between questionnaire score of eating severity and rCBF in left insula. |
| Pujol et al. 2014 [53] | Resting state fMRI | 24 adults with PWS (12 males, mean 26.3 y) 20 adults with Down’s syndrome (10 males, mean 24.5 y) 20 adults with William’s syndrome (11 males, mean 25.2 y) 80 young adults (45 males, mean 26.4 y) 71 children (30 males, mean 9.6 y) 53 older adults (24 males, mean 67.4 y) |
Young adults showed sensorimotor system activity positively correlating with motion, suggesting system specific effects. Seen to some extent in children and older adults but also wider effects of motion. Greater motion in genetic disorders, and specific motion-connectivity correlations: PWS group shoed mostly frontal and temporal lobe correlations with motion, but also significant in the dorsal ACC; in Down’s syndrome group was with anterior and dorsal regions; and in William’s syndrome were diffuse correlations across grey matter voxels. |
| Shapira et al. 2005 [54] | fMRI: before and after glucose load. | 3 participants with PWS (1 male, 25–38 y) | Delay in activation of brain areas associated in satiety response in previous study of participants without PWS, including hypothalamus, insula, ventromedial PFC and nucleus accumbens following oral glucose load. |
| Stauder et al. 2002 [55] | EEG: P3 ERP response to visual and auditory oddball tasks. | 10 adults with PWS (5 males, mean 30.8 y) 10 typically-developing controls (3 males, mean 23.2 y) |
Markedly decreased P3 response in both visual and auditory tasks in PWS compared to control group, and most strongly for the auditory task. |
| Stauder et al. 2005 [56] | EEG: N200 and P300 ERPs during response inhibition on Go-Nogo task. | 11 participants with deletion subtype of PWS (7 males, mean 26.7 y) 11 participants with UPD subtype of PWS (4 males, mean 27.7 y) 11 typically-developing control participants (6 males, mean 27.3 y) |
Behavioural task performance poorer for both PWS groups compared to control group. N200 amplitude didn’t show normal peak in either PWS group, suggesting impaired early modality specific inhibition in both UPD and deletion, but only UPD group showed impaired P300 modulation, indicative of later general inhibition. |
| Woodcock et al. 2010 [57] | fMRI: set-shifting task. | 8 participants with PWS (5 males, mean 20.7 y) 8 age & gender matched typically-developing control participants (mean 21 y) |
Control group showed increased activity compared to the PWS group in frontoparietal regions during switching, including in ventromedial PFC and posterior parietal cortex. PWS tended to show ventromedial PFC deactivation instead. Group interactions: Greater activity in hippocampus, amygdala, thalamus and putamen during switching in control group than PWS group, driven by deactivation of these areas by PWS group during switching alongside activation in the control group. The reverse pattern was found for the anterior poles. |
| Zhang et al. 2013 [58] | Resting state fMRI | 21 participants with PWS (11 males, mean 7.3 y) 18 sibling control participants (8 males, mean 11.1 y) |
ALFF greater in PWS than control group in ventrolateral PFC, ACC, inferior parietal lobe and left insula, and decreased in the medial and dorsolateral PFC, hippocampus, pre- and post-central gyri, and left OFC. DMN: reduced functional connectivity pairwise between medial PFC, inferior parietal lobe and precuneus, and between precuneus and inferior parietal lobe. PFC network: reduced functional connectivity between dorsolateral PFC and OFC, and increased functional connectivity between ventrolateral PFC and both OFC and dorsolateral PFC. Core network: increased ACC-insula functional connectivity. Motor sensory network: decrease pre- to post-central gyrus connectivity. |
| Zhang et al. 2012 (see also 2015) [59,60] | Resting state fMRI | 21 participants with PWS (11 males, mean 7.3 y) 18 sibling control participants (8 males, mean 11.1y) |
ALFF increased in PWS in ACC, hypothalamus, & left amygdala and decreased in medial PFC and right amygdala. Granger causality analysis of direction of connectivity: Increased causal influence bilaterally from amygdala to the hypothalamus, from the ACC to the medial PFC right amygdala, from the medial PFC to bilateral amygdala, & from ACC to medial PFC in PWS compared to control participants. Altered directionality in effective connectivity in all pairwise analyses except the right amygdala to hypothalamus, although this increased in strength. |
ACC: anterior cingulate cortex; ALFF: amplitude of low frequency fluctuation; AS: Angelman’s syndrome; BMI: body mass index; EEG: electroencephalography; ERP: event-related potential; fMRI: functional magnetic resonance imaging; ID: intellectual disability; m: months; OFC: orbitofrontal cortex; PET: positron emission tomography; PFC: prefrontal cortex; PWS: Prader-Willi syndrome; rCBF: regional cerebral blood flow; UPD: uniparental disomy; y: years.