Voxel-based morphometry: current perspectives

Figures & data

Table 1 Single-case VBM studies

Study	Subject	Disease	Number of control subjects	GM increase or decrease	Brain regions	Anatomoclinical correlation
Taubert et al, 2015^Citation113	27♂ 28♂ 30♂ 14♂	Top athlete	46	Increase	Putamen + thalamus Putamen + caudatus Putamen + caudatus	UK
Martinaud et al, 2015^Citation114	14♀	Developmental visual impairment	30	Decrease	R ventral occipitotemporal region, bilateral cingulate sulcus, paracentral lobule, SMA	Yes
Luedecke et al, 2014^Citation115	50♂	Presenilin 1 mutation		Decrease	Precuneus, parietal lobe, the R hippocampus	Yes
Kitamura et al, 2014^Citation116	72♂	REM sleep behavior disorder	UK	Decrease	Tegmental portion of the pons, anterior lobes of the cerebellum, hippocampus	UK
Serino et al, 2014^Citation117	44♂	Electrocution-induced heart attack	10	Decrease	R precuneus	UK
Yasuno et al, 2014^Citation118	30♂	TBI	13	Decrease	Bilateral insular cortex, posterior cingulate cortex, hypothalamus, R parietal cortex, medial occipital cortex	Yes
Yao et al, 2013^Citation119	14♂	Isolated congenital anosmia	20	Decrease	L OFC, precuneus, gyrur rectus, middle cingulate cortex, thalamus, subcallosal gyrus, fusiform gyrus	Yes
Migliaccio et al, 2012^Citation120	Seven subjects (6♀)	PCA	29	Decrease	Bilateral ventral occipital and temporal (three of seven patients), R supramarginal gyrus (two of seven patients), bilateral inferior parietal lobule (seven of seven patients)	Yes
Beeson et al, 2011^Citation121	67♂	PPA	35	Decrease	Bilateral posterior perisylvian regions, bilateral mild lateral temporal lobes	Yes
Klingner et al, 2011^Citation122	23♂	Bell palsy	I	Decrease	L MI, bilateral SMA, L insula, bilateral cerebellum	Yes
Migliaccio et al, 2011^Citation123	58♀	PCA	I5	Decrease	Bilateral superior occipital gyrus, cuneus, bilateral inferior occipital gyrus, bilateral lingual gyrus, bilateral superior parietal lobule, bilateral thalamus	Yes
Sehm et al, 2011^Citation124	24♂	Focal retrograde amnesia	20	Decrease	L temporopolar cortex, R lingual cortex	Yes
Valdes-Sosa et al, 2011^Citation125	73♂	Prosopagnosia	10	Decrease	L ventral and occipital temporal cortex, L fusiform gyrus	Yes
Bianchini et al, 2010^Citation126	22♂	Topographical disorientation	12	–	–	–
Eriguchi et al, 2010^Citation127	31♂	Citrullinemia epilepsy	111	Decrease	L hippocampus	UK
Freudermann et al, 2010^Citation128	72♀	Vascular encephalopathy	7	Decrease increase	R postcentral, R IPL, bilateral putamen, L cingulated cortex	UK
Maguire et al, 2010^Citation129	70♂	SD	10	Decrease	L striatum, LSTG, bilateral hippocampus, L IFG, R temporal pole, R cerebellum, R ITG	No
Nanri et al, 2010^Citation130	84♂	Autoimmune ataxia + Basedow disease	–	Decrease	R cerebellar cortex	Yes
Riddoch et al, 2010^Citation131	74♀ 70♂ 65♂	Stroke	140	Decrease	R IPL, R IFG, R angular, R supramarginal gyrus, R parietooccipital regions, L parietotemporal regions, R IFG, R STG, R supramarginal, R angular gyrus	Yes
Rigoni et al, 2010^Citation107	24♀	Psychopathy	6	Decrease	L MFG, L SFG, L lateral temporal cortex, L superior occipital cortex, L SFG, L MFG	Yes
Muhlau et al, 2009^1^Citation32	22 subjects (12♀)	HD	133 for each subject	Decrease	Bilateral head of caudate, R insula, R temporal pole	UK
Narvid et al, 2009^Citation133	66♂	FTD + HME	28	Decrease	R ventral and medial frontal cortex, R insular cortex	Yes
Tramoni et al, 2009^Citation134	34♂	Functional amnesia	25 subjects (10♀)	–	–	–
Bozzalli et al, 2008^Citation135	77♀	CBD	8	Decrease	Bilateral pre- and post-central gyrus, R middle frontal gyrus, L middle frontal gyrus, R SFG, R IFG, R Puntamen, R lenticular nucleus, R parietal lobe	Yes
Epelbaum et al, 2008^Citation136	46♂	Pure alexia, epilepsy	17	Decrease	Bilateral frontal and ACC, L parietal gyrus	UK
Feldman et al, 2008^Citation137	54♂	PCA	20	Decrease	R occipital mesial and inferior, R fusiform, R ACC, R SFG, R precuneus, L occipital inferior gyrus	Yes
Adlam et al, 2006^Citation138	Six subjects	PPA	12	Decrease	L ventral temporal lobe (three of six subjects), L dorsoventral temporal lobe (two of six subjects), R temporal pole (one of six subjects), R rostroventral temporal lobe (one of six subjects)	Yes
Brazdil et al, 2006^Citation139	25♀	Epilepsy	–	Increase	Anterior rim of the L central sulcus	UK
Cipollotti et al, 2006^Citation140	74♂	Hippocampal amnesia	15	Decrease	Bilateral head of body of hippocampus and entorhinal cortex	Yes
Colliot et al, 2006^Citation141	27 subjects (16♀)	FCD	39	Increase Increase Decrease	Regions with FCD lesions (21/27 patients), frontal and temporal extralesional regions (16/27 patients), frontal and temporal extralesional regions (eight of 27 patients)	UK
Joubert et al, 2006^Citation142	61♀ 59♀ 73♂	Right FTD	28	Decrease	R inferior temporal gyrus, R hippocampus, R middle temporal gyrus, R caudate, L STG	Yes
Suzuki et al, 2005^Citation143	43♂ 32♂ 38♂ 44♀ 36♀	Schizophrenia	20 (10♀)	Decrease	L IFG and L frontal pole (four patients only)	Yes
Zahn et al, 2005^Citation144	Ten subjects (6♀) Five subjects (1♀)	AD PPA	10 (5♀)	Decrease	Bilateral anterior lateral temporal (eight of ten AD and five of five PPA); L medial temporal (nine AD and one PPA); R posterior parietal (nine AD and five PPA); R posterior cingulate and R precuneus (nine AD and zero PPA)	Yes
Gorno-Tempini et al, 2004a^Citation145	56♀	PPA + CBD	16	Decrease	L IFG, L anterior insula, L SMA, bilateral caudate	Yes
Gorno-Tempini et al, 2004b^Citation146	67♀	Right SD	35	Decrease	R anterior temporal lobe, R amygdala/anterior hippocampus, R collateral sulcus, R fusiform gyrus, R posterior insula/STG, L amygdala/anterior hippocampus, L collateral sulcus/fusiform gyrus	Yes
Thompson et al, 2004^Citation147	64♂ 66	SD FTD	17	Decrease	L infero lateral temporal lobe, L ACC, L insula, R temporal pole	Yes
Salmond et al, 2003^Citation148	14 subjects (1♀)	Autism	18 (12♀)	Decrease	Bilateral hippocampus (in seven subjects), amygdala, OFC (in 13 subjects), STG, cerebellum (in eleven subjects)	No
Rosen et al, 2002^Citation149	54♀ 81♂ 65♂	PPA AD SD	20 for each subject	Decrease	L DLPFC, L IFG, bilateral temporoparietal cortex, bilateral IPL, L anterior temporal	Yes
Gitelman et al, 2001^Citation150	33♀ 38♂ 416^1 56♀ 71♀	Herpes simplex	10 for each subject	Decrease	Bilateral amygdala, hippocampus, entorhinal cortex, insula, gyrus rectus, nucleus accumbens	UK
Mummery et al, 2000^Citation151	Six subjects (5♀)	SD	14	Decrease	Bilateral temporal pole, L middle temporal gyrus, bilateral amygdala, bilateral fusiform gyrus	Yes
Woerman et al, 1999^Citation152	20 subjects (12♀)	JME	30 subjects (16♀)	Increase decrease	Bilateral temporoposterior lobe (two of 20 subjects); bilateral frontopolar areas (three of 20 subjects)	UK

Notes: Anatomoclinical correlation column refers to the existence of a correspondence between the brain regions emerged from the analysis and the clinical symptoms manifested by the patients. For each manuscript, “yes” or “no” is reported based on whether the anatomoclinical correlation has been highlighted and explained by the authors. When this correspondence has not been evaluated, “UK” (unknown) is reported in the table. ♂, male; ♀, female.

Abbreviations: L, left; R, right; UK, unknown; REM, rapid eye movements; TBI, traumatic brain injury; PPA, primary progressive aphasia; PCA, posterior cortical atrophy; SD, semantic dementia; HD, Huntington disease; FTD, frontotemporal dementia; FTD, frontotemporal dementia; CBD, corticobasal degeneration; AD, Alzheimer’s disease; HME, hereditary multiple exostoses; JME, Jouvenile myoclonic epilepsy; FCD, focal cortical dysplasia; IPL, inferior parietal lobule; SMA, supplementary motor area; M1, primary motor area; MFG, medial frontal gyrus; STG, superior temporal gyrus; ITG, inferior temporal gyrus; IFG, inferior frontal gyrus; SFG, superior frontal gyrus; ACC, anterior cingulate cortex; OFC, orbitofrontal cortex; DLPFC, dorsolateral prefrontal cortex; FWE, family-wise error; FDR, false discovery rate; TIV, total intracranial volume.

Figure 1 Distribution of false positives in parametric and nonparametric single-case VBM.

Notes: In the top panel, the figure represents the percentage of false positives found in each brain regions when using parametric statistics with P=0.05 FWE correction: colors reflected the percentage of false positives (adapted from Neuroimage, 70, Scarpazza C, Sartori G, De Simone M, Mechelli A, When the single matters more than the group: very high false positive rates in single case voxel based morphometry, 175–188,⁹¹ Copyright ©2013, with permission from Elsevier.). In the bottom panel, the figure represents the localization of false positives based on peak coordinates with P=0.05 FWE correction (adapted from Scarpazza C, Nichols T, Seramondi D, Maumet C, Sartori G, MechelliA. When the single matters more than the group (II): addressing the problem of high false positive rates in single case voxel based morphometry using non-parametric statistics. Front Neurosci. 2016;10:6.⁹²): colors reflected the different brain regions in which the false positives were found to be located. In both panels, (A) GM increases in the single subject compared with the control group at P<0.05 corrected and (B) GM decreases in the single subject compared with the control group at P<0.05 corrected.

Abbreviations: VBM, voxel-based morphometry; FWE, family-wise error; GM, gray matter.

Figure 2 Example of single-case VBM.

Notes: The figure represents (A) the localization of false positives when investigating the decrease of GM in a single subject compared with a control group (in which the light blue means the absence of false positives, the blue a false-positive rate from 0.5% to 5%, and the green a false-positive rate from 5.5% to 10%) and (B) the localization of significant findings in a murderer compared with a control group (Rigoni et al¹⁰⁷). (A) Adapted from Neuroimage, 70, Scarpazza C, Sartori G, De Simone M, Mechelli A, When the single matters more than the group: very high false positive rates in single case voxel based morphometry, 175–188,⁹¹ Copyright ©2013, with permission from Elsevier.

Abbreviations: VBM, voxel-based morphometry; GM, gray matter.

Figure 3 The risk of reverse inference.

Notes: (A) Author’s brain compared with 16 controls (Reprinted from Neuroimage, 70, Scarpazza C, Sartori G, De Simone M, Mechelli A, When the single matters more than the group: very high false positive rates in single case voxel based morphometry, 175–188,⁹¹ Copyright ©2013, with permission from Elsevier). The significant cluster denotes increased GM in the single brain compared to controls located in the dorsolateral prefrontal cortex. According to Scarpazza et al,⁹¹ this cluster has up to 10% of likelihood to be a false positive. (B) Smaller GM volume in binge drinkers compared with healthy controls, adapted from Doallo S, Cadaveira F, Corral M, Mota N, López-Caneda E, Holguín S. Larger mid-dorsolateral prefrontal gray matter volume in young binge drinkers revealed by voxel-based morphometry. PLoS One. 2014;9(5):e96380.¹¹² The significant cluster is located in the dorsolateral prefrontal cortex.

Abbreviation: GM, gray matter.

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