One of the most fascinating phenomena of the human mind is the cognitive process by which an individual’s experiences of themselves and their body are integrated (Orfei et al. 2007). Nevertheless, neurological damage can lead to anomalies in the perception and representation of one's own body, such as in the case of personal neglect (PN). Patients suffering from PN behave as if the contralesional part of their body does not exist. For example, they might appear with only half of their face shaved or made up, their hair combed only on the ipsilesional side, or with their glasses misplaced on the contralesional side of their head. They might only wear a slipper or an earring on the ipsilesional side. Even their posture may suggest indifference relating to the contralesional side of their body, as both standing and sitting, they tend to place themselves in the so-called “three quarter” position, with the ipsilesional part of the body leaning forward and the contralesional part left behind. This frequently results in accidents and traumas which are due to the patient neglecting the position of their body, and it may also negatively impact on motor recovery (Committeri et al. 2018).
In the first reports of patients displaying PN, their failure to explore the contralesional parts of the body was described (Zingerle 1913; Cutting 1978). Since then, subsequent definitions have maintained this aspect as the main focus of the condition (e.g. Beschin and Robertson 1997; McIntosh et al. 2000; Committeri et al. 2007; Caggiano et al. 2014), although various other, specific aspects have been referred to, such as patients’ inability to recognise and use their paretic limbs (in the absence of severe motor deficits, Guariglia and Antonucci 1992; Iosa et al. 2016; Cocchini and Beschin 2020), or to orient their attention towards the contralesional side of their body (Marangolo et al. 2003; de Vignemont 2010; Ronchi et al. 2018) or mentally represent only this part of their body (Bisiach and Luzzati 1978; Baas et al. 2011; Reinhart et al. 2012; Di Vita et al. 2017).
PN has been also described in terms of hemisomatoagnosia (or asomatognosia, Vallar 1998; Vallar and Calzolari, 2018), namely, as a lack of awareness of the contralesional body part. Nevertheless, several experimental studies have shown the existence of dissociations between the two clinical conditions (Moro et al. 2004; Spinazzola et al. 2020), although they are both typically present as consequences of strokes in the right hemisphere. For example, patients with personal neglect (but without asomatognosia) recognise their contralateral limb when it is moved so that they can see it in the ipsilesional space (Moro et al., 2004). Conversely, patients suffering from asomatognosia do not recognise the arm as their own (Jenkinson et al. 2018) even when their attention is focused on that body part. Specifically, asomatognosia refers to a disturbance relating to the feeling of ownership of the affected body part, with patients reporting seeing it fading or disappearing or missing completely. These symptoms are not present in PN.
Dissociations have also been reported in cases of extrapersonal neglect, when there is a consistent reduction in the processing of information coming from the contralesional side of external space in comparison with the information coming from the ipsilesional side (Cubelli 2017). Dissociations have been found both during clinical assessments (Guariglia and Antonucci 1992; Baas et al. 2011; Di Vita et al. 2017) and in studies of lesional correlates (Committeri et al. 2018). In a recent review of the literature on the topic (Caggiano and Jehkonen, 2018), it appears that PN is less frequently diagnosed than extrapersonal neglect, although a frequency of 30.8% is reported in patients with right hemispheric lesions. A lack of adequate tests to evaluate the condition has probably also contributed to the syndrome being underestimated in the past (Guariglia and Antonucci 1992; Committeri et al. 2018). In addition, PN is often associated with other deficits (such as motor, somatosensory and visual field deficits, extrapersonal neglect and anosognosia for hemiplegia) and these may make the symptoms difficult to isolate.
The hypothesis at the basis of the present study is that PN is a disconnection syndrome which is not associated with discrete grey matter lesions, but instead involves a right hemisphere network of cortical and subcortical structures contributing to body representation. Related disconnection hypotheses have been recently supported in other syndromes, such as spatial neglect (Thiebaut de Schotten et al. 2005), anosognosia for hemiplegia (Pacella et al. 2019; Monai et al. 2020) and disorders in the sensations of body ownership (Moro et al. preprint).
Previous neuroanatomical data on PN correlates also support this hypothesis, since they suggest a role played by multimodal areas (i.e. temporo-parietal junction, Baas et al. 2011; Catani & Ffytche 2005) and the underlying white matter connections (Baas et al. 2011; Committeri et al. 2007) in the syndrome, along with lesions in the perirolandic, superior temporal and inferior parietal gyri (Azouvi et al. 2002; Roussaeaux et al. 2015).
However, a certain degree of ambiguity persists in these results, for several reasons. Firstly, to date neuroanatomical studies on PN have been conducted on small samples, with a maximum of 30 patients presenting with the symptoms; these have often been compared to left hemisphere damaged patients (Azouvi et al. 2002; Buxbaum et al. 2004; Committeri et al. 2007; Baas et al. 2011; Rousseaux et al. 2015; Caggiano et al. 2020). Furthermore, the results of these studies focused on the identification of discreet cortical lesions and did not analyse white matter disconnections in a specific way. Finally, co-occurrent neuropsychological symptoms are usually considered in clinical comparisons between groups of patients with and without PN symptoms, but not directly entered into neuroanatomical analyses as covariates, or alternative models of causation.
The present study aimed to overcome these limitations by investigating the neural correlates of PN in a sample of 104 right hemisphere damaged patients, 68 of whom showed a pathological score in a validated, neuropsychological test assessing PN (Comb subtest of the Comb and Razor test, McIntosh et al. 2000). A Multivariate Voxel Lesion Symptoms Mapping approach (LESYMAP) with sparse canonical correlations (Mirman et al. 2018) was used to identify the grey matter structures whose lesions correlate with PN symptoms in the whole group. The multivariate approach is considered to be statistically and conceptually more adequate than the univariate counterparts for lesion analyses. Indeed, while the univariate Voxel Lesion Symptom Mapping techniques assume independency among voxels, the Multivariate Voxel Lesion Symptom Mapping approach detects which group of voxels together contribute to the emergence of behavioural deficits, assuming a statistical dependency (Pustina et al., 2018). This approach allows to consider that lesions usually extend to more than a voxel and, consequently, the probability that a voxel is lesioned is dependent on the probability of surrounding voxels conditions. For the white matter, the Tractotron software (Foulon et al., 2018) was used to identify the probability of disconnections for each known tract and each patient, taking into account the contribution of clinical and neuropsychological variables. Lastly, a series of linear models were performed, and comparisons were made in order to identify which of the structures resulting from the anatomical analyses explain PN more clearly than the clinical symptoms, and to ascertain whether these are integrated in a network.