Table 2.

Comparison between brain areas affected by reduced glucose metabolism, volume and energy metabolism in insulin resistance (IR), Alzheimer’s disease (AD-vulnerable brain regions) and migraine (migraine-vulnerable brain regions).

Brain areas	Reduced regional cerebral glucose metabolism in subjects with insulin resistance	Reduced regional cerebral glucose metabolism in migraine subjects	Reduced regional cerebral energy metabolismin migraine subjects ***	Reduced regional cerebral volume in migraine subjects	Alzheimer’s disease - vulnerable brain regions
The insular lobe		Insular lobe: CM [50]Insular cortex: EM [48], CM [49]		Insular lobe: † [51], [52]Insular cortex: *CM [53]
The parietal lobe	Parietal lobe: [54] lateralParietal cortex: †††† [55] leftBrodmann areas 7 and 40: [56]	Parietal cortex: CM [49]	↓ PCr/Pi ¯ [57]↓ [Mg+2] ¯ [58]↓ PCr/Pi ¯ [59]	Parietal lobe: CM [53]Parietal operculum: † CM [51] left	Parietal lobe: [60-62]Parietal cortex: [43]Parieto-temporal cortex: [63]Inferior parietal cortex: [64]
The anterior cingulate cortex		Anterior cingulate cortex: CM [49], [48]		Anterior cingulate cortex: ** EM e CM [65], † CM [51], CM [66], [67] right, [52]
The posterior cingulate cortex	Posterior cingulate cortex: [56]	Posterior cingulate cortex: EM [48]			Posterior cingulate cortex: [60-64, 68]
The temporal lobe	Temporal lobe: [54]Middle temporal cortex: †††† [55] leftTemporal/angular gyri (Brodmann area 39): [56]	Inferior temporal, temporal pole, right-banks superior temporal sulcus: CM [50]	↓ PCr/Pi ¯ [57]↓ [Mg+2 ] ¯ [58]↓ PCr/Pi ¯ [59]	Temporal pole, superior temporal lobe: CM [66] Left superior temporal gyrus, right fusiform gyrus, right middle temporal gyrus: CM [69]Superior temporal sulcus left, inferior temporal gyrus left : CM [69]	Temporal lobe: [43, 60]Temporal cortex: [64, 68] lateral, [70]Inferior temporal gyrus: [71]Temporopolar cortex: [64]
The prefrontal cortex	Prefrontal cortex:[54]Anterior and inferior prefrontal cortices (Brodmann areas 10, 45, 47): [56]	Prefrontal cortex: EM [48] leftPars triangularis (Brodmann areas 44): CM [50] Orbitofrontal cortex (Brodmann area 10, 11 and 47)****: CM [49]Orbitofrontal (Brodman area 47)††: CM [50] left		Inferior frontal gyri (Brodmann areas 44, 45, 47)*****:CM [51]†, EM [72], [67]Dorsolateral prefrontal cortex (Brodmann areas 46 and 9): EM [65, 73]Pars triangularis (Brodmann areas 44): CM [66]Lateral orbital frontal cortex (Brodman area 47)††: CM [69, 74, 75] left, ††† CM [76]Medial orbital frontal gyrus: CM [66]	Prefrontal Cortex [43]Inferior frontal cortex (Brodmann areas 44, 45, 47)*****: [64]
The frontal lobe	Superior frontal gyrus: †††† [55] right Middle frontal gyrus: †††† [55]	Superior frontal gyrus: CM [50] leftFrontal pole: CM [50] right Precentral gyrus: CM [50] right	↓ PCr/Pi ¯ [57]↓ Pi/Tp ¯ [57]↓ [Mg+2] ¯ [58]↓PCr/Pi ¯ [59]	Medial frontal lobes: ††† CM [76]Superior frontal gyrus: CM [75]Middle frontal gyrus: [67], CM [53] caudal Precentral gyrus: CM [53, 69, 72], [67] rightRight frontal pole: CM [74],††† [76]	Frontal lobes: [60, 61, 63]Superior frontal gyrus: [68]Middle frontal gyrus: [68, 71]
The hippocampus	Hippocampus: [55]			Hippocampus: CM [65, 77] leftEntorhinal cortex: CM [66]Parahippocampal gyrus: [67] leftParahippocampus:EM [72]	Hippocampus: [43, 60, 62, 64, 68, 78-81]Entorhinal cortex:[64, 68, 81]Parahippocampal gyrus:[68]
The amygdala	Amygdala: [55]			Amygdala: † [51, 82] left	Amygdala: [61, 68, 78, 81]
The occipital lobe			↓ PCr/Pi ¯, ↓ [Mg+2 ] ¯ [82]

EM	episodic migraine
CM	chronic migraine
PCr	phosphocreatine
Pi	inorganic phosphate
TP	total phosphorus signal
PCr/Pi, PCr/ATP	a reduced ratio indicates energy deficit
ATP	adenosine triphosphate
In bold	brain areas affected by reduced glucose metabolism and shared by insulin resistance, migraine and AD subjects.
*	Lai KL et al enrolled patients with CM without medication overuse headache, major depression or prior preventive treatment.
**	A higher headache frequency was associated with smaller grey matter volume in the anterior cingulate cortex and hippocampus in EM and CM
***	According to current literature, most studies have chosen the occipital cortex as the region of interest, as aura, most commonly with visual symptoms, is attributed to this area in patients suffering from this type of migraine [83]
****	The orbitofrontal cortex includes the Brodmann areas 10, 11 and 47 [84]
*****	The inferior frontal gyrus includes the Brodmann areas 44, 45 and 47 [85]
†	In comparing the brains of CM patients with EM patients, Valfrè et al reported that CM patients had significant grey matter reductions in these areas.
††	The lateral orbital gyrus includes the Brodmann area 47 [86] Mackey, Sott; Petrides, Michael (2006). "Chapter 2: The orbitofrontal cortex: sulcal and gyral morphology and architecture". In Zald, David H.; Rauch, Scott (eds.). The Orbitofrontal Cortex. New York: Oxford University Press. p. 34
†††	Chronic migraine patients had smaller frontal regions than episodic migraine patients.
††††	This study on young women with Polycystic Ovary Syndrome reported a direct association between mild insulin resistance and brain glucose hypometabolism, which was independent of overweight or obesity.