In 1874, Karl Kahlbaum described
catatonia as an independent syndrome characterized by motor, affective, and behavioral anomalies. In the following years, various
catatonia concepts were established with all sharing the prime focus on motor and behavioral symptoms while largely neglecting affective changes. In 21st century,
catatonia is a well-characterized clinical syndrome. Yet, its neurobiological origin is still not clear because methodological shortcomings of hitherto studies had hampered this challenging effort. To fully capture the clinical picture of
catatonia as emphasized by Karl Kahlbaum, 2 decades ago a new
catatonia scale was developed (Northoff
Catatonia Rating Scale [NCRS]). Since then, studies have used NCRS to allow for a more mechanistic insight of
catatonia. Here, we undertook a systematic review searching for neuroimaging studies using motor/behavioral
catatonia rating scales/criteria and NCRS published up to March 31, 2019. We included 19 neuroimaging studies. Studies using motor/behavioral
catatonia rating scales/criteria depict cortical and subcortical motor regions mediated by
dopamine as neuronal and biochemical substrates of
catatonia. In contrast, studies relying on NCRS found rather aberrant higher-order frontoparietal networks which, biochemically, are insufficiently modulated by
gamma-aminobutyric acid (
GABA)-ergic and glutamatergic transmission. This is further supported by the high therapeutic efficacy of
GABAergic agents in acute
catatonia. In sum, this systematic review points out the difference between motor/behavioral and NCRS-based classification of
catatonia on both neuronal and biochemical grounds. That highlights the importance of Kahlbaum's original truly psychomotor concept of
catatonia for guiding both research and clinical diagnosis and
therapy.