Table 3:

Multimodal imaging, metabolites, and cognition in schizophrenia

Author	n (control/ patient)	Illness stage	Medication status	Cognitive domain (all are fMRI tasks)	Region	Tesla	Metabolite	Acquisition	MRS Sequence	TE (ms)	Reference	Metabolite level group difference	Associations between metabolites and fMRI
(Fusar-Poli et al., 2011)	17/24	ARMS	naïve	Verbal fluency task	ACC, left hippocampus and left thalamus	3	Glu	SV	PRESS	30	W	↓Glu in thalamus	Thalamic Glu levels were negatively associated with activation in the right DLPFC and left orbitofrontal cortex, but positively associated with activation in the right hippocampus and the bilateral temporal cortex in ARMS; opposite pattern seen in HC.
(Valli et al., 2011)	14/22	ARMS	naïve	Verbal episodic memory task	ACC, medial temporal cortex, and thalamus	3	Glu	SV	PRESS	30	W	Not reported	Medial temporal Glu was positively associated with medial temporal activation during the episodic memory task in HC; opposite pattern seen in ARMS.
(Hutcheson et al., 2012)	28/28	Chronic	Medicated	Memory retrieval	Left hippocampus	3	Glx	SV	PRESS	80	Cr	-	Hippocampal Glx was positively correlated with the left IFG BOLD response during memory retrieval in HC, but not SZ
(Falkenberg et al., 2014)	17/17	Chronic	Medicated	Bergen dichotic listening task	dorsal ACC	3	Glu	SV	PRESS	35	Cr	↓Glu	Positive correlations between Glu and BOLD in inferior parietal in SZ; opposite pattern in HC.
(Allen et al., 2015)	27/33	UHR	mixed	Verbal fluency task	Left thalamus	3	Glu	SV	PRESS	30	W	-	UHR subjects with poor functional outcome showed negative relationship between thalamic glutamate levels and prefrontal striatal activation, pattern not seen in those with good functioning and HC
(Overbeek et al., 2019)	21/17	FEP	Medicated	RBANS, Stroop test	ACC	7	Glu, Gln, GABA	SV	STEAM	5	W	↓Glu	ACC GABA was negatively correlated with Stroop effect reaction time. In FEP, the relationship between ACC Glu and BOLD response in the DMN was opposite to HC
(White et al., 2015)	19/22	Chronic	Medicated	Prediction error task	SN	3	Glx	SV	PRESS	80	Cr	↑Glx	In HC, but not in SZ, prediction error BOLD response was positively associated with SN Glx
(Cadena et al., 2018)	20/22	Chronic	Un-medicated	Stroop task	ACC	3	Glx	SV	PRESS	80	Cr	-	In SZ, the relationship between ACC Glx and BOLD in regions of the salience network and posterior DMN was opposite to HC

↑ Metabolite level is higher in patients than controls; ↓ Metabolite level is lower in patients than controls; - no group differences in metabolite levels

Abbreviations:

n: number of subjects; ARMS: at risk mental state; FEP: first episode psychosis patients; SZ: patients with schizophrenia; UHR: ultra high risk patients; HC: healthy controls

TE: Echo Time; SV: single voxel spectroscopy; PRESS: Point Resolved Spectroscopy; STEAM: STimulated Echo Acquisition Mode; W: water; Cr: creatine; Glu: glutamate; Gln: glutamine; Glx: glutamate+ glutamine; GABA: γ-aminobutyric acid

ACC: anterior cingulate cortex; BOLD: blood oxygen level dependent signal; DLPFC: dorsolateral prefrontal cortex; DMN: default mode network; SN: substantia nigra