Table 1.
Putative network targets for experimental therapies aimed at promoting recovery of consciousness
| Target network | Network nodes | Pharmacologic | Electromagnetic | Mechanical | Sensory | Regenerative |
|---|---|---|---|---|---|---|
| Ascending arousal network | mRt, VTA, LC, PTg, PnO, PBC, LDTg, DR, MnR, PAG, IL, Ret, TMN, LHA, SUM, NBM, DBB | DA, NE, 5HT, ACh, Glu, GABA, Ox, nonspecific | DBS, PNS | LIFUP | Vestibular, tactile, auditory | Stem cells, neurogenesis, gliogenesis, axonal regrowth |
| Default mode network | PCC, Pr, vMPFC, dMPFC, IPL, HF, LTC, Th | TMS, tES | LIFUP | – | ||
| Salience network (ventral attention network) | dACC, FI, AI, SLEA, PAG, TP, SN, VTA, Hy, Put, dmTh, antTh | – | – | Auditory, tactile, vestibular | ||
| Dorsal attention network | FEF, IPS, SPL, aMT | – | – | – | ||
| Executive control network (frontoparietal network) | dLPFC, dMPFC, vLPFC, LP, dCN | TMS, tES | – | – | ||
| Thalamocortical network | IL, cerebral cortex | DBS | LIFUP | – | ||
| Limbic network | OF, TP | – | – | Auditory | ||
| Somatomotor network | S1, M1, SMA, PMC | TMS, tES, PNS | – | Tactile, vestibular | ||
| Visual network | V1, V2, V3, V4 | – | – | – | ||
| Auditory network | STG, IFG | – | – | Auditory |
Canonical neural networks that have been characterized in the human brain are listed in the first column. Network nodes and neuroanatomic abbreviations are listed in the second column, based upon recent network-based studies [235–240]. The five types of therapeutic modalities characterized in this gap analysis are listed in subsequent columns, and the putative network targets of each therapy are listed in the individual cells of the table. Of note, there are ongoing debates about the incorporation of specific nodes in certain networks (e.g., the inclusion of the thalamus in the DMN)
5HT 5-hydroxytryptamine (serotonin), ACh acetylcholine, AI anterior insula, aMT anterior middle temporal area complex, antTh anterior thalamus, DA dopamine, dACC dorsal anterior cingulate cortex, DBB diagonal band of Broca, DBS deep brain stimulation, dCN dorsal caudate nucleus, dLPFC dorsolateral prefrontal cortex, DMN default mode network, dMPFC dorsomedial prefrontal cortex, dmTh dorsomedial thalamus, DR dorsal raphe, FEF frontal eye fields, FI frontoinsular cortex, GABA γ-aminobutyric acid, Glu glutamate, Hy hypothalamus, HF hippocampal formation, IFG inferior frontal gyrus, IL intralaminar nuclei of thalamus, IPL inferior parietal lobule, IPS intraparietal sulcus, LC locus coeruleus, LDTg laterodorsal tegmental nucleus, LHA lateral hypothalamic area, LIFUP low-intensity focused ultrasound pulsation, LP lateral parietal cortex, LTC lateral temporal cortex, M1 primary motor cortex, MnR median raphe, MNS median nerve stimulation, mRt midbrain reticular formation, NBM nucleus basalis of Meynert, NE norepinephrine, OF orbitofrontal cortex, Ox orexin, PAG periaqueductal gray, PBC parabrachial complex, PCC posterior cingulate cortex, PMC premotor cortex, PnO pontis oralis (i.e., pontine reticular formation), PNS peripheral nerve stimulation, Pr precuneus, PTg pedunculopontine tegmental nucleus, Put putamen, Ret reticular nucleus of the thalamus, S1 primary somatosensory cortex, SLEA sublenticular extended amygdala, SMA supplementary motor area, SN substantia nigra, SPL superior parietal lobule, STG superior temporal gyrus, SUM supramammillary nucleus of the hypothalamus, tES transcranial electrical stimulation, Th thalamus, TMN tuberomammillary nucleus of the hypothalamus, TMS transcranial magnetic stimulation, TP temporal pole, vLPFC ventrolateral prefrontal cortex, vMPFC ventromedial prefrontal cortex, V1, V2, V3, V4 primary and association visual cortices, VTA ventral tegmental area