Elisabetta Làdavas

Hemispatial neglect Subtypes, neuroanatomy, and disability

Objective: To assess the relative frequency of occurrence of motor, perceptual, peripersonal, and personal neglect subtypes, the association of neglect and other related deficits (e.g., deficient nonlateralized attention, anosognosia), and the neuroanatomic substrates of neglect in patients with right hemisphere stroke in rehabilitation settings. Methods: The authors assessed 166 rehabilitation inpatients and outpatients with right hemisphere stroke with measures of neglect and neglect subtypes, attention, motor and sensory function, functional disability, and family burden. Detailed lesion analyses were also performed. Results: Neglect was present in 48% of right hemisphere stroke patients. Patients with neglect had more motor impairment, sensory dysfunction, visual extinction, basic (nonlateralized) attention deficit, and anosognosia than did patients without neglect. Personal neglect occurred in 1% and peripersonal neglect in 27%, motor neglect in 17%, and perceptual neglect in 21%. Neglect severity predicted scores on the Functional Independence Measure and Family Burden Questionnaire more accurately than did number of lesioned regions. Conclusions: The neglect syndrome per se, rather than overall stroke severity, predicts poor outcome in right hemisphere stroke. Dissociations between tasks assessing neglect subtypes support the existence of these subtypes. Finally, neglect results from lesions at various loci within a distributed system mediating several aspects of attention and spatiomotor performance.

Selective deficit in personal moral judgment following damage to ventromedial prefrontal cortex

Recent fMRI evidence has detected increased medial prefrontal activation during contemplation of personal moral dilemmas compared to impersonal ones, which suggests that this cortical region plays a role in personal moral judgment. However, functional imaging results cannot definitively establish that a brain area is necessary for a particular cognitive process. This requires evidence from lesion techniques, such as studies of human patients with focal brain damage. Here, we tested 7 patients with lesions in the ventromedial prefrontal cortex and 12 healthy individuals in personal moral dilemmas, impersonal moral dilemmas and non-moral dilemmas. Compared to normal controls, patients were more willing to judge personal moral violations as acceptable behaviors in personal moral dilemmas, and they did so more quickly. In contrast, their performance in impersonal and non-moral dilemmas was comparable to that of controls. These results indicate that the ventromedial prefrontal cortex is necessary to oppose personal moral violations, possibly by mediating anticipatory, self-focused, emotional reactions that may exert strong influence on moral choice and behavior.

Seeing where your hands are

Some patients with brain damage fail to identify a sensory stimulus presented on the opposite side to their lesion (contralesional) when a competing stimulus is presented on the same side (ipsilesional). This phenomenon has become known as extinction. It is commonly studied using a single sense such as sight or touch (unimodal extinction). We have studied a 75-year-old right-handed man (patient GS) who has severe left tactile extinction resulting from damage to the right frontotemporal cortex caused by a stroke. We found that an ipsilesional visual stimulus could induce extinction of a contralesional tactile stimulus (cross-modal extinction). We also found that the visual stimulus operates in a reference system attached to the hand, and not in egocentric coordinates (that is retinal, head or trunk-centred coordinates).

Neuropsychological Evidence of an Integrated Visuotactile Representation of Peripersonal Space in Humans

Current interpretations of extinction suggest that the disorder is due to an unbalanced competition between ipsilesional and contralesional representations of space. The question addressed in this study is whether the competition between left and right representations of space in one sensory modality (i.e., touch) can be reduced or exacerbated by the activation of an intact spatial representation in a different modality that is functionally linked to the damaged representation (i.e., vision). This hypothesis was tested in 10 right-hemisphere lesioned patients who suffered from reliable tactile extinction. We found that a visual stimulus presented near the patients ipsilesional hand (i.e., visual peripersonal space) inhibited the processing of a tactile stimulus delivered on the contralesional hand (cross-modal visuotactile extinction) to the same extent as did an ipsilesional tactile stimulation (unimodal tactile extinction). It was also found that a visual stimulus presented near the contralesional hand improved the detection of a tactile stimulus applied to the same hand. In striking contrast, less modulatory effects of vision on touch perception were observed when a visual stimulus was presented far from the space immediately around the patients hand (i.e., extrapersonal space). This study clearly demonstrates the existence of a visual peripersonal space centered on the hand in humans and its modulatory effects on tactile perception. These findings are explained by referring to the activity of bimodal neurons in premotor and parietal cortex of macaque, which have tactile receptive fields on the hand and corresponding visual receptive fields in the space immediately adjacent to the tactile fields.

Ameliorating neglect with prism adaptation: visuo-manual and visuo-verbal measures.

Previous studies have shown that adaptation to rightward displacing prisms improves performance of neglect patients on visuo-manual (VM) tasks such as line cancellation, figure copying, and line bisection [Nature 395 (1998) 166]. The present study further evaluated the effect of prism adaptation (PA) on neglect symptoms by investigating: (a) the range of beneficial effects on common visuo-spatial deficits as well as less frequent phenomena like neglect dyslexia; (b) the duration of improvement following a single exposure to the right optical deviation; (c) the extent to which visuo-spatial performance can be comparatively ameliorated in VM tasks and visuo-verbal (VV) tasks (i.e. involving or not the adapted arm, respectively) and (d) the presence and duration of the manual visuo-motor bias induced by the prismatic adaptation (i.e. the after-effect). We investigated these issues in a group of neglect patients with right hemispheric damage who were also affected by neglect dyslexia. Following a single, brief prismatic adaptation the results showed that (a) several visuo-spatial abilities, including accuracy in reading single words and non-words, considerably improved, (b) the amelioration was long-lasting, continuing for at least 24h, (c) the presence, amount, and duration of neglect amelioration was not limited to VM tasks, but extended to VV tasks and (d) the presence and duration of the after-effect induced by prismatic adaptation remarkably paralleled the presence and duration of the improvement of neglect symptoms. These findings clearly demonstrate that beneficial effects induced by a single PA are very long-lasting and spread over a wide range of visuo-spatial deficits, independent of the type of response required. In addition, our results strongly suggest that the process of adaptation, as revealed by the presence of a visuo-motor after-effect, might be essential for establishing amelioration. In light of its characteristics, the prismatic adaptation technique should be a priority tool for the rehabilitation of the multifaceted hemispatial neglect syndrome.

Functional and dynamic properties of visual peripersonal space

In order to code visual peripersonal space, human and non-human primates need an integrated system that controls both visual and tactile inputs within peripersonal space around the face and the hand, based on visual experience of body parts. The existence of such a system in humans has been demonstrated, and there is evidence showing that visual peripersonal space relating to the hand has important dynamic properties, for example, it can be expanded and contracted depending on tool use. There is also evidence for a high degree of functional similarity between the characteristics of the visual peripersonal space in humans and in monkeys.

Patterns of spontaneous recovery of neglect and associated disorders in acute right brain-damaged patients

Objectives: The evolutionary pattern of spontaneous recovery from acute neglect was studied by assessing cognitive deficits and motor impairments. Detailed lesion reconstruction was also performed to correlate the presence of and recovery from neglect to neural substrates. Methods: A consecutive series of right brain-damaged (RBD) patients with and without neglect underwent weekly tests in the acute phase of the illness. The battery assessed neglect deficits, neglect-related deficits, and motor impairment. Age-matched normal subjects were also investigated to ascertain the presence of non lateralised attentional deficits. Some neglect patients were also available for later investigation during the chronic phase of their illness. Results: Partial recovery of neglect deficits was observed at the end of the acute period and during the chronic phase. Spatial attention was impaired in acute neglect patients, while non spatial attentional deficits were present in RBD patients with and without acute neglect. A strong association was found between acute neglect and fronto-parietal lesions. Similar lesions were associated with neglect persistence. In the chronic stage, neglect recovery was paralleled by improved motor control of the contralesional upper limb, thus emphasising that neglect is a negative prognostic factor in motor functional recovery. Conclusions: These findings show that spatial attention deficits partially improve during the acute phase of the disease in less than half the patients investigated. There was an improvement in left visuospatial neglect at a later, chronic stage of the disease, but this recovery was not complete.

Implicit associative priming in a patient with left visual neglect.

Recent studies have suggested that patients with visual neglect may process, even if without awareness, perceptual features of the neglected stimuli. The aim of the current study was to further investigate whether the ignored stimuli are processed at a deeper level. Findings from a patient with damage to the right hemisphere and with left visual neglect (no hemianopia) are reported. He showed an associative priming in the neglected space: response to a word in the right visual field was faster when the word was preceded by the brief presentation of an associated word in the neglected field. When obliged to orient attention to the left side of a computer screen, he was not able to detect the presence of, to read aloud, or to judge the lexical status and semantic content of left-sided stimuli. This patient was able to perform a covert post-perceptual processing of the neglected stimuli, but could not do so when explicitly requested.

The Regulation of Cognitive Control following Rostral Anterior Cingulate Cortex Lesion in Humans

The contribution of the medial prefrontal cortex, particularly the anterior cingulate cortex (ACC), to cognitive control remains controversial. Here, we examined whether the rostral ACC is necessary for reactive adjustments in cognitive control following the occurrence of response conflict [Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. Conflict monitoring and cognitive control. Psychological Review, 108, 624652, 2001]. To this end, we assessed 8 patients with focal lesions involving the rostral sector of the ACC (rACC patients), 6 patients with lesions outside the frontal cortex (non-FC patients), and 11 healthy subjects on a variant of the Simon task in which levels of conflict were manipulated on a trial-by-trial basis. More specifically, we compared Simon effects (i.e., the difference in performance between congruent and incongruent trials) on trials that were preceded by high-conflict (i.e., incongruent) trials with those on trials that were preceded by low-conflict (i.e., congruent) trials. Normal controls and non-FC patients showed a reduction of the Simon effect when the preceding trial was incongruent, suggestive of an increase in cognitive control in response to the occurrence of response conflict. In contrast, rACC patients attained comparable Simon effects following congruent and incongruent events, indicating a failure to modulate their performance depending on the conflict level generated by the preceding trial. Furthermore, damage to the rostral ACC impaired the posterror slowing, a further behavioral phenomenon indicating reactive adjustments in cognitive control. These results provide insights into the functional organization of the medial prefrontal cortex in humans and its role in the dynamic regulation of cognitive control.

Automatic and voluntary orienting of attention in patients with visual neglect: Horizontal and vertical dimensions

The present study was aimed at testing internally and externally-controlled mechanisms of covert orienting in patients with visuo-spatial neglect. Internally-controlled orienting was tested by presenting central informative cues. Externally-controlled orienting was tested by presenting peripheral non-informative cues. We also tested for the presence of vertical neglect in patients with horizontal neglect, and tried to assess whether altitudinal neglect is an attentional deficit. Finally we examined whether altitudinal neglect manifests itself only in the visual field contralateral to the lesion or, as has been shown for horizontal neglect, whether it is also present in the ipsilesional visual field. The results showed that patients with neglect have a deficit of externally-controlled covert orienting in the visual field opposite to that of the lesion. Further, the impairment appeared to be more pronounced in the lower than in the upper visual field and to be mainly evident in the visual field contralateral to the lesion. The deficit could, however, be partially compensated for by the use of internally-controlled covert orienting. These findings seems to support the dual-mechanisms hypothesis which maintains that automatic and voluntary orienting are subserved by separate mechanisms possibly located in different parts of the brain.