Alien Hand, Restless Brain: Salience Network and Interhemispheric Connectivity Disruption Parallel Emergence and Extinction of Diagonistic Dyspraxia

Abstract

Diagonistic dyspraxia (DD) is by far the most spectacular manifestation reported by sufferers of acute corpus callosum (CC) injury (so-called “split-brain”). In this form of alien hand syndrome, one hand acts at cross purposes with the other “against the patient’s will”. Although recent models view DD as a disorder of motor control, there is still little information regarding its neural underpinnings, due to widespread connectivity changes produced by CC insult, and the obstacle that non-volitional movements represent for task-based functional neuroimaging studies. Here, we studied patient AM, the first report of DD in patient with complete developmental CC agenesis. This unique case also offers the opportunity to study the resting-state connectomics of DD in the absence of diffuse changes subsequent to CC injury or surgery. AM developed DD following status epilepticus (SE) which resolved over a 2-year period. Whole brain functional connectivity (FC) was compared (Crawford-Howell [CH]) to 16 controls during the period of acute DD symptoms (Time 1) and after remission (Time 2). Whole brain graph theoretical models were also constructed and topological efficiency examined. At Time 1, disrupted FC was observed in inter-hemispheric and intra-hemispheric right edges, involving frontal superior and midline structures. Graph analysis indicated disruption of the efficiency of salience and right frontoparietal (FP) networks. At Time 2, after remission of diagnostic dyspraxia symptoms, FC and salience network changes had resolved. In sum, longitudinal analysis of connectivity in AM indicates that DD behaviors could result from disruption of systems that support the experience and control of volitional movements and the ability to generate appropriate behavioral responses to salient stimuli. This also raises the possibility that changes to large-scale functional architecture revealed by resting-state functional magnetic resonance imaging (fMRI) (rs-fMRI) may provide relevant information on the evolution of behavioral syndromes in addition to that provided by structural and task-based functional imaging.

Interlimb Transfer of Reach Adaptation Does Not Require an Intact Corpus Callosum: Evidence from Patients with Callosal Lesions and Agenesis

“…1 D ) and posterior commissure, left hippocampal sclerosis, and a history of complex partial seizures in the setting of mesial temporal lobe epilepsy. Full patient details can be found in Ridley et al (2016) , but in summary, AM endured status epilepticus in March 2012. One month later, despite full resolution of epileptic seizures, AM developed intermanual conflicts: for instance, when putting on a pair of trousers with the left hand, the right hand would pull them off ( Ridley et al, 2016 ).…”

“…Full patient details can be found in Ridley et al (2016) , but in summary, AM endured status epilepticus in March 2012. One month later, despite full resolution of epileptic seizures, AM developed intermanual conflicts: for instance, when putting on a pair of trousers with the left hand, the right hand would pull them off ( Ridley et al, 2016 ). Neuropsychological assessment revealed right-sided constructional apraxia, right ideomotor apraxia and right visual anomia, showing signs of interhemispheric disconnection.…”

A Critical Review of Alien Limb-Related Phenomena and Implications for Functional Magnetic Resonance Imaging Studies

“…Table 3 lists the brain regions activated upon involuntary movements as indicated by fMRI studies performed in patients with AL and in patients with other movement disorders (i.e., Huntington's disease and Parkinson's disease) where resting tremor and dyskinesia were mainly investigated by means of resting-state approaches ( 48 , 86 , 87 ) instead of using task-related fMRI.…”

The structural basis for interhemispheric functional connectivity: Evidence from individuals with agenesis of the corpus callosum

“…Lastly, we used topographic theory on DTI and rs-fMRI data to study the global SC and FC at the network level in AgCC and HC. VMHC quantifies the FC between each voxel in one hemisphere and its mirrored counterpart in the other hemisphere ( Hung et al, 2019 , Owen et al, 2013b , Ridley et al, 2016 ). Graph-based approaches model the brain as a complex network represented graphically by a collection of nodes and edges.…”