Lesion network localization of free will

Abstract

Our perception of free will is composed of a desire to act (volition) and a sense of responsibility for our actions (agency). Brain damage can disrupt these processes, but which regions are most important for free will perception remains unclear. Here, we study focal brain lesions that disrupt volition, causing akinetic mutism (n = 28), or disrupt agency, causing alien limb syndrome (n = 50), to better localize these processes in the human brain. Lesion locations causing either syndrome were highly heterogeneous, occurring in a variety of different brain locations. We next used a recently validated technique termed lesion network mapping to determine whether these heterogeneous lesion locations localized to specific brain networks. Lesion locations causing akinetic mutism all fell within one network, defined by connectivity to the anterior cingulate cortex. Lesion locations causing alien limb fell within a separate network, defined by connectivity to the precuneus. Both findings were specific for these syndromes compared with brain lesions causing similar physical impairments but without disordered free will. Finally, our lesion-based localization matched network localization for brain stimulation locations that disrupt free will and neuroimaging abnormalities in patients with psychiatric disorders of free will without overt brain lesions. Collectively, our results demonstrate that lesions in different locations causing disordered volition and agency localize to unique brain networks, lending insight into the neuroanatomical substrate of free will perception. free will | agency | volition | functional connectivity | lesions

Reply: Heterogeneous neuroimaging findings, damage propagation and connectivity: an integrative view

“…For instance, patients with behavioral variant frontotemporal dementia can have either tau or TDP-43 pathology, and patients with corticobasal syndrome can have either tau or Alzheimer's pathology, yet these different pathologies result in similar clinical symptoms and localize to the same brain network. Second, we found common network localization for delusions in patients with brain lesions and Alzheimer's disease (Darby et al, 2018a), and for disordered free will perception in patients with brain lesions and psychiatric diseases like catatonia, non-epileptic seizures, and conversion disorder (Darby et al, 2018b). These results and others support the idea that neuropsychiatric symptoms localize to common brain networks regardless of the underlying pathology or diagnosis.…”

Mapping Symptoms to Brain Networks with the Human Connectome

“…Although anatomical connectomes can be used for this purpose, 5,11 most studies have used functional connectomes in order to incorporate the widest possible network that is connected polysynaptically rather than in a simpler point-to-point manner. 13,14,[36][37][38][39][40][41][42][43] Network maps that are derived from lesions in different patients with the same or similar symptoms are then overlapped or compared statistically to identify connections common to these symptoms (Fig. 3F).…”

“…These include auditory hallucinations, 14 aphasia, 14 pain, 14 hemichorea, 37 parkinsonism, 42 impaired decision making, 36 delusions of familiarity, 38 freezing of gait, 39 criminality, 13 coma, 40 and disorders of volition and agency. 41,43 In each case, lesions in different locations that cause the same symptom are part of a single brain network, defined by their functional connectivity. These results of lesion network mapping are reproducible across independent groups of patients with lesions that cause the same symptom 13,37,38,44 and are specific when compared with lesions that cause different symptoms.…”

“…The relevance of lesion network mapping for patients with symptoms who have no associated destructive brain lesions also remains uncertain, but there have been provocative findings. 37,43 For example, lesion locations that cause hallucinations are connected to regions that are hyperactive in patients with schizophrenia, in which there are no consistent brain lesions, who have hallucinations. 14,15 However, the clinical features of hallucinations differ between patients with schizophrenia and those with focal brain lesions, and patients with schizophrenia have functionalneuroimaging abnormalities that extend well beyond the implicated networks.…”

Disconnectome Associated with Progressive Ischemic Periventricular White Matter Lesions

“…The use of a virtual lesion approach to identify pathways altered by PVWM is an extension of the "lesion network mapping" approach (48), which uses patients' traced lesions on healthy subjects' functional connectivity to identify the connections associated with the patients' symptoms. Lesion network mapping has thus far been applied primarily to focal lesions such as stroke (49).…”