The clinical course, prognosis, and quality of life of individuals with schizophrenia are associated with the severity of negative symptoms which are defined as deficiencies in the areas of motivation, emotion, and communication (Green et al., 2012). An improved understanding of the underlying neuropathology of negative symptoms may aid in developing better treatments for this unmet therapeutic need (Rabinowitz et al., 2012; Robertson et al., 2014).

Studies of the pathophysiology underlying the broad construct of negative symptoms have failed to show consistent findings, ostensibly due to heterogeneity between different negative symptom constructs (Galderisi et al., 2018). Negative symptoms form a hierarchical structure with two second-order dimensions [motivation and pleasure (MAP), diminished expression (EXP)] and five first-order domains (anhedonia, avolition, and asociality, blunted affect and alogia) (Strauss et al., 2019a, 2019b, 2018). We assert that examining associations between these negative symptom dimensions and domains and brain imaging measures will be informative regarding their pathophysiology, advancing efforts to develop more refined treatments targeting specific symptom domains.

Abnormalities in resting-state brain activity are robust in schizophrenia. Amplitude of low frequency fluctuations (ALFF)—a resting-state brain activity measure obtained from functional magnetic resonance imaging (fMRI) data—is computed as the average square root of the power spectrum within a frequency band at each brain voxel, yielding a measure of the average amplitude of blood oxygen level dependent (BOLD) signal fluctuations over time. It can also be normalized by the power of the entire frequency range resulting in fractional ALFF (fALFF). ALFF is sensitive to baseline cerebral blood flow and reflects spontaneous and intrinsic neural activity (Zhou et al., 2010).

A meta-analysis found that ALFF is lower in somatosensory cortex, posterior parietal cortex, and occipital cortex, and is higher in bilateral striatum, medial temporal cortex, and medial prefrontal cortex in schizophrenia compared to controls (Xu et al., 2015). There is also evidence of associations between ALFF and hallucinations (Hare et al., 2018, 2017). However, associations between regional ALFF and negative symptoms remain to be determined.

One study found that deficit schizophrenia (DS), characterized by primary and persistent negative symptoms, compared to non-deficit schizophrenia (NDS) exhibited lower fALFF in the left insula and frontotemporal cortex, bilateral insula, and anterior cingulate gyrus, and greater fALFF in the bilateral visual cortex (Zhou et al., 2019). Another found a positive association between right putamen ALFF and a negative association between left cerebellum ALFF and total negative symptom severity in DS but not NDS (Li et al., 2017). However, these studies did not examine associations between ALFF and negative symptom subdomains. This study examined, to our knowledge for the first time, the associations between ALFF and dimensions and domains of negative symptoms.