Raffaella Ricci

The anatomy of anosognosia for hemiplegia: a meta-analysis.

Anosognosia for hemiplegia is the denial of the contralesional motor deficits that may follow brain damage. Although this disturbance has been reported in the neurological literature since the beginning of the last century, only few longitudinal studies have addressed the issue of the anatomical substrate of the disorder. Here we present a comprehensive review of the literature on anosognosia for hemiplegia from 1938 to 2001, taking into account some of its clinical, epidemiological and anatomical aspects. In particular, an attempt has been made to identify the intra-hemispheric lesion locations most frequently associated to the denial behaviour. Our review shows that anosognosia for hemiplegia most frequently occurs in association to unilateral right-sided or bilateral lesions of different brain areas (cortical and/or subcortical). It seems to be equally frequent when the damage is confined to frontal, parietal or temporal cortical structures, and may also emerge as a consequence of subcortical lesions. Interestingly, the probability of occurrence of anosognosia is highest when the lesion involves parietal and frontal structures in combination, if compared to other combinations of lesioned areas. This pattern of lesions suggests the existence of a complex cortico-subcortical circuit underlying awareness of motor acts that, if damaged, can give raise to the anosognosic symptoms.

Perceptual and Response Bias in Unilateral Neglect: Two Modified Versions of the Milner Landmark Task ☆ ☆☆

Perceptual and response bias in estimating the proportion of the two segments of prebisected lines were disambiguated in a group of 121 patients suffering from left neglect by means of two variants of the Milner Landmark task (Milner et al., 1993). The first variant, LANDMARK-V, required a verbal response; the second variant, LANDMARK-M, required manual pointing. The paper reports and discusses the results obtained on each task and their correlations, as well as the relationships between either kind of bias and the intrahemispheric location of the lesion. It is argued that besides their usefulness as a diagnostic tool the proposed variants of the Milner Landmark task provide results that are worth further investigation in their own right.

Visual awareness and anisometry of space representation in unilateral neglect: A panoramic investigation by means of a line extension task

UNLABELLED Ninety-one right brain-damaged patients with left neglect and 43 right brain-damaged patients without neglect were asked to extend horizontal segments, either left- or rightward, starting from their right or left endpoints, respectively. Earlier experiments based on similar tasks had shown, in left neglect patients, a tendency to overextend segments toward the left side. This seemingly paradoxical phenomenon was held to undermine current explanations of unilateral neglect. The results of the present extensive research demonstrate that contralesional overextension is also evident in most right brain-damaged patients without contralesional neglect. Furthermore, they show that in a minority of left neglect patients, the opposite behavior, i.e., right overextension can be found. The paper also reports the results of correlational analyses comprising the parameters of line-extension, line-bisection, and cancellation tasks, as well as the parameters relative to the Milner Landmark Task, by which a distinction is drawn between perceptual and response biases in unilateral neglect. A working hypothesis is then advanced about the brain dysfunction underlying neglect and an attempt is made at finding an explanation of neglect and the links between the mechanisms of space representation and consciousness through the study of the changes induced by unilateral brain lesions in the characteristics of space-coding neurons. ABBREVIATIONS C, control group; GN+91, full group of neglect patients; GN+27, group of neglect patients with relative left overextension; GN+14, group of neglect patients with relative right overextension; GN-43, full group of non-neglect patients; GN-9, group of non-neglect patients with relative left overextension; H canc, H cancellation task; LE, left extension; LE/RE, ratio of left-right extension; N+, neglect patients; N-, non-neglect patients; PB Land-M, perceptual bias on Landmark motor task; PB Land-V, perceptual bias on Landmark verbal task; RB Land-M, response bias on Landmark motor task; RB Land-V, response bias on Landmark verbal task; RE, right extension.

Focal electrical stimulation as a sham control for repetitive transcranial magnetic stimulation: Does it truly mimic the cutaneous sensation and pain of active prefrontal repetitive transcranial magnetic stimulation?

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is a novel, noninvasive method of stimulating selected regions of the brain that has both research applications and potential clinical utility, particularly for depression. To conduct high-quality clinical studies of rTMS, it is necessary to have a convincing placebo (or sham) treatment. Prefrontal rTMS causes cutaneous discomfort and muscle twitching; therefore, an optimal control condition, ie, sham condition, would mimic the cutaneous sensation and muscular discomfort of rTMS without stimulating the brain. Ideally, the quality and intensity of the sham condition would feel identical to the quality and intensity of the rTMS condition, except that the sham would have no effect on cortical activity. We designed and built a focal electrical stimulation system as a sham rTMS condition. Although this electrical sham system is superior to methods used in previous studies, little is known about how the new electrical sham system compares with active rTMS in terms of the level of discomfort and type of sensation it produces. METHODS We hypothesized that the electrical sham system may not mirror the experimental condition sufficiently. We studied this hypothesis under single-blind conditions in 15 healthy adults by administering either the real or sham rTMS at high and low intensities while subjects, who were unaware of condition, rated subjective qualities of the stimulation (such as tingling, pinching, and piercing), the scalp location of the perception, and the painfulness of the stimuli. RESULTS At low-intensity stimulation, the two techniques (active and sham) differ with respect to the subjective quality of the sensation. The differences between real and sham rTMS were less dramatic at higher intensities. The best sham condition that most closely mimics real prefrontal rTMS requires individual titration of the intensity of electrical stimulation across a broad range. Performing this titration without unblinding patients is likely possible, but technically challenging. We propose a new approach to do this. CONCLUSION We conclude that it is possible to create a truly indistinguishable sham condition (with appropriate acoustic masking as well), but more work is needed beyond these initial attempts.

Quantitative Analysis of Cancellation Tasks in Neglect

Patients with spatial neglect do not explore contralateral space effectively. Although cancellation tasks are used widely to assess this visual search deficit, their methods of analysis are not well established. We introduce logistic regression analyses for cancellation tasks in 7 patients with left neglect. We investigated the influences of spatial location, stimuli number, and target discriminability on the probability of canceling a target. As a group, neglect patients showed left and near neglect. They also explored and canceled targets further into contralateral space on arrays with fewer visual stimuli. Individual analyses revealed exceptions to these group patterns, such as two patients with far rather than near neglect. Only patients with relatively mild neglect canceled more targets when they were more easily discriminated from distracters. Logistic regression models accounted for 0.68 the variance in cancellation performances of the entire group. Shifting the unit of analysis from the proportion of targets canceled to the probability of detecting individual targets offers a powerful parametric method to analyze group and individual performances on cancellation tasks and can reveal functional dissociations in neglect.

Imaging the neural mechanisms of TMS neglect-like bias in healthy volunteers with the interleaved TMS/fMRI technique: preliminary evidence

Applying a precisely timed pulse of transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC) can produce temporary visuo-spatial neglect-like effects. Although the TMS is applied over PPC, it is not clear what other brain regions are involved. We applied TMS within a functional magnetic resonance imaging (fMRI) scanner to investigate brain activity during TMS induction of neglect-like bias in three healthy volunteers, while they performed a line bisection judgment task (i.e., the landmark task). Single-pulse TMS at 115% of motor threshold was applied 150 ms after the visual stimulus onset. Participants completed two different TMS/fMRI sessions while performing this task: one session while single-pulse TMS was intermittently and time-locked applied to the right PPC and a control session with TMS positioned over the vertex. Perceptual rightward bias was observed when TMS was delivered over the right PPC. During neglect-like behavior, the fMRI maps showed decreased neural activity within parieto-frontal areas, which are often lesioned or dysfunctional in patients with left neglect. Vertex TMS induced behavioral effects compatible with leftward response bias and increased BOLD signal in the left caudate (a site which has been linked to response bias). These results are discussed in relation to recent findings on neural networks subserving attention in space.

Cerebral cortex plasticity after 90 days of bed rest: data from TMS and fMRI.

INTRODUCTION Microgravity animal models have demonstrated corticospinal plasticity; however, little is understood of its functional significance. In this pilot study, we explored corticospinal plasticity in a bed rest model. We hypothesized that the lack of weight bearing would induce cortical reorganization correlating with performance. METHODS Four subjects underwent functional MRI (fMRI), transcranial magnetic stimulation (TMS), and functional mobility testing (FMT) before and after 90 d of bed rest. Recruitment curves (RC) were created by measuring motor evoked potentials over a range of TMS intensities with changes in the slope of the RC reflecting changes in corticospinal excitability. RESULTS Significant leg RC slope decreases were observed on post-bed rest day 1 (P1) (t(2805) = -4.14, P < 0.0001), P2 (t(2805) = -6.59, P < 0.0001), P3 (t(2805) = -6.15, P < 0.0001), P5 (t(2805) = -7.93, P <0.0001), P8 (t(2805) = -3.30, P = 0.001), and P12 (t(2805)= -3.33, P = 0.0009), suggesting a group decrease in corticospinal excitability in the immediate post-bed rest period with recovery approaching baseline over the following 2 wk. Significant effects were observed for hand RC slopes only for P2 (t(2916) = 1.97, P = 0.049), P3 (t(2916) = -2.12, P = 0.034), and P12 (t(2916) = -2.19, P = 0.029); no significant effects were observed for days P0 (t(2916) = -1.32, ns), P1 (t(2916) = 1.00, ns), P5 (t(2916) = -0.21, ns), or P8 (t(2916) = -0.27, ns). fMRI showed no change in activation for the hand but an increase in activation post-bed rest for the leg. On an individual basis, a more heterogeneous response was found which showed a potential association with performance on FMT. DISCUSSION Results of this research include a better understanding of the cortical plasticity associated with leg disuse and may lead to applications in patient and astronaut rehabilitation.

Sensory and response contributions to visual awareness in extinction

Abstract.Brain-damaged patients may extinguish contralesional stimuli when ipsilesional stimuli are presented simultaneously. Most theories of extinction postulate that stimuli compete for pathologically limited attentional resources with a bias to process ipsilesional over contralesional stimuli. Implicit in this view is the idea that responses follow the outcome of an earlier competition between inputs. In the current study of two patients, we used signal detection analyses to test the hypothesis that response criteria and response modalities also contribute to visual awareness. We found that identification was more sensitive than detection in uncovering deficits of contralesional awareness. Extinction was worse with bilateral stimuli when the ipsilesional stimulus was identical or similar to the target than when it was dissimilar. This diminished awareness was more likely to reflect a shift towards more conservative responses rather than diminished discrimination of contralesional stimuli. By contrast, one patient was better able to discriminate contralesional stimuli when using his contralesional limb to indicate awareness of targets than when using his ipsilesional limb. These data indicate that the nature of stimuli can modulate response criteria and the motor response can affect the sensory discriminability. Sensory discrimination and response output are not organized in a simple serial manner. Rather, input and output parameters interact in complicated ways to produce visual awareness. Visual awareness itself appears to be the outcome of two bottlenecks in processing, one having to do with sensory processing that may be covert and the other having to do with decision making, which by definition is overt. Finally, we advocate the use of signal detection analyses in studies of extinction, a method that has been surprisingly neglected in this line of research.

Using interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (fMRI) and dynamic causal modeling to understand the discrete circuit specific changes of medications: lamotrigine and valproic acid changes in motor or prefrontal effective connectivity.

The purpose of this study was to use interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (TMS/fMRI) to investigate the effects of lamotrigine (LTG) and valproic acid (VPA) on effective connectivity within motor and corticolimbic circuits. In this randomized, double-blind, crossover trial, 30 healthy volunteers received either drug or placebo 3.5 h prior to interleaved TMS/fMRI. We utilized dynamic causal modeling (DCM) to assess changes in the endogenous effective connectivity of bidirectional networks in the motor-sensory system and corticolimbic circuit. Results indicate that both LTG and VPA have network-specific effects. When TMS was applied over the motor cortex, both LTG and VPA reduced TMS-specific effective connectivity between primary motor (M1) and pre-motor cortex (PMd), and between M1 and the supplementary area motor (SMA). When TMS was applied over prefrontal cortex, however, LTG alone increased TMS-specific effective connectivity between the left dorsolateral prefrontal cortex(DLPFC) and the anterior cingulate cortex (ACC). In summary, LTG and VPA inhibited effective connectivity in motor circuits, but LTG alone increased effective connectivity in prefrontal circuits. These results suggest that interleaved TMS/fMRI can assess region- and circuit-specific effects of medications or interventions.

Effects of illusory spatial anisometry in unilateral neglect

Patients with visuospatial neglect tend to underestimate horizontal magnitudes in contralesional space. It has been recently hypothesised that this behaviour might be due to anisometry of space perception, by which horizontal stimuli would be progressively underestimated proceeding from the ipsi towards the contralesional side of space. We investigated the effects of modulating space perception through the Oppel-Kundt illusion (i.e. a filled space is perceived as more expanded than an empty space) on the behaviour of 28 neglect patients and 28 normal subjects. The two groups bisected lines on backgrounds of vertical lines evenly spaced or unevenly spaced, with distances which decreased progressively from one side of the page to the other. On the same backgrounds, they extended segments to the left or to the right so as to double them. Patients also had to cancel targets, the density of which was evenly distributed or horizontally increased from one side of the page to the other. Both groups were prone to the illusion. Neglect bias was modulated by the illusion in the expected direction. It was reduced when the illusion induced a perceptual distortion opposite to that thought to underlie neglect. On bisection and cancellation tasks, illusory effects were greater in patients with higher values of response bias on the Milner Landmark task. These findings, taken together with patients’ anatomical data, suggest that a modulation of neglect through a visual illusion can normally be induced in patients with relatively intact visual input processes.