Marilena Aiello

Damage to White Matter Pathways in Subacute and Chronic Spatial Neglect: A Group Study and 2 Single-Case Studies with Complete Virtual “In Vivo” Tractography Dissection

The exact anatomical localization of right hemisphere lesions that lead to left spatial neglect is still debated. The effect of confounding factors such as acute diaschisis and hypoperfusion, visual field defects, and lesion size may account for conflicting results that have been reported in the literature. Here, we present a comprehensive anatomical investigation of the gray- and white matter lesion correlates of left spatial neglect, which was run in a sample 58 patients with subacute or chronic vascular strokes in the territory of the right middle cerebral artery. Standard voxel-based correlates confirmed the role played by lesions in the posterior parietal cortex (supramarginal gyrus, angular gyrus, and temporal-parietal junction), in the frontal cortex (frontal eye field, middle and inferior frontal gyrus), and in the underlying parietal-frontal white matter. Using a new diffusion tensor imaging-based atlas of the human brain, we were able to run, for the first time, a detailed analysis of the lesion involvement of subcortical white matter pathways. The results of this analysis revealed that, among the different pathways linking parietal with frontal areas, damage to the second branch of the superior longitudinal fasciculus (SLF II) was the best predictor of left spatial neglect. The group study also revealed a subsample of patients with neglect due to focal lesion in the lateral-dorsal portion of the thalamus, which connects the premotor cortex with the inferior parietal lobule. The relevance of fronto-parietal disconnection was further supported by complete in vivo tractography dissection of white matter pathways in 2 patients, one with and the other without signs of neglect. These 2 patients were studied both in the acute phase and 1 year after stroke and were perfectly matched for age, handedness, stroke onset, lesion size, and for cortical lesion involvement. Taken together, the results of the present study support the hypothesis that anatomical disconnections leading to a functional breakdown of parietal-frontal networks are an important pathophysiological factor leading to chronic left spatial neglect. Here, we propose that different loci of SLF disconnection on the rostro-caudal axis can also be associated with disconnection of short-range white matter pathways within the frontal or parietal areas. Such different local disconnection patterns can play a role in the important clinical variability of the neglect syndrome.

No inherent left and right side in human ‘mental number line’: evidence from right brain damage

Spatial reasoning has a relevant role in mathematics and helps daily computational activities. It is widely assumed that in cultures with left-to-right reading, numbers are organized along the mental equivalent of a ruler, the mental number line, with small magnitudes located to the left of larger ones. Patients with right brain damage can disregard smaller numbers while mentally setting the midpoint of number intervals. This has been interpreted as a sign of spatial neglect for numbers on the left side of the mental number line and taken as a strong argument for the intrinsic left-to-right organization of the mental number line. Here, we put forward the understanding of this cognitive disability by discovering that patients with right brain damage disregard smaller numbers both when these are mapped on the left side of the mental number line and on the right side of an imagined clock face. This shows that the right hemisphere supports the representation of small numerical magnitudes independently from their mapping on the left or the right side of a spatial-mental layout. In addition, the study of the anatomical correlates through voxel-based lesion-symptom mapping and the mapping of lesion peaks on the diffusion tensor imaging-based reconstruction of white matter pathways showed that the rightward bias in the imagined clock-face was correlated with lesions of high-level middle temporal visual areas that code stimuli in object-centred spatial coordinates, i.e. stimuli that, like a clock face, have an inherent left and right side. In contrast, bias towards higher numbers on the mental number line was linked to white matter damage in the frontal component of the parietal-frontal number network. These anatomical findings show that the human brain does not represent the mental number line as an object with an inherent left and right side. We conclude that the bias towards higher numbers in the mental bisection of number intervals does not depend on left side spatial, imagery or object-centred neglect and that it rather depends on disruption of an abstract non-spatial representation of small numerical magnitudes.

Spatial orienting biases in the decimal numeral system.

Humans map numbers upon a mental number line (MNL) on which small integers are placed to the left of larger ones [1-9]. Here, we show that human adults systematically shift the subjective midpoints of number intervals away from the borders separating contiguous tens along the MNL. Number intervals are erroneously bisected further to the right the closer they are to the left starting point of the tens and further to the left the closer they are to the right endpoint of the tens. Similarly, right-brain-damaged patients neglecting the left side of the MNL [10-12] show enhanced pathological rightward deviation in the bisection of number intervals located toward the left starting point of the tens and reduced deviation for intervals located toward the right endpoint of the tens. These data disclose the effects that the recursive grouping of symbolic decimal numerals within the tens has brought on the phylogenetically and ontogenetically foregoing spatial representation of magnitudes [13-16].

Neglect “around the clock”: Dissociating number and spatial neglect in right brain damage

Publisher Summary This chapter examines the link between number and the spatial biases observed in spatial neglect. Right-brain-damaged patients affected by left unilateral neglect are characterized by a pathological attentional bias to the right side of space. This left-sided deficit encompasses eye and head deviations, visual, somatosensory and auditory sensory processing, action initiation and realization, and mental representations. The spatial cueing effect arising in the external space coordinates was present irrespective of the emphasis in the instructions either concerning fingers or side of space. Neglect patient populations manifested a clear-cut double dissociation. Some of the patients displayed very severe neglect on the bisection of visual lines and normal performance for the bisection of number intervals. The increasing rightward error displayed by D participants in the bisection of large 7-unit intervals located to the “left” side of decades offers another example of the apparent similarity between bisection behavior in visual and number space. Another point that needs careful consideration when one discusses the associations and dissociations between numerical and spatial coding that can be observed in the healthy brain is whether the influence of numerical cues on spatial processing is as strong as the reciprocal influence of spatial cues on number processing.

Small numbers in the right brain: evidence from patients without and with spatial neglect.

Sissa e Cognitive Neuroscience Sector, Trieste, ItalyFollowing seminal introspective evidence reported by Galton(1880), several investigations have suggested that peoplewith left-to-right reading habits, mentally organize numbersalong the equivalent of a horizontal ruler, the mental numberline (MNL), with small magnitudes located to the left of largerones(Seronet al., 1992; Dehaene et al.,1993; Sagivet al., 2006).A recent finding considered in agreement with this evidence,shows a pathological bias toward numbers that are higherthan the true midpoint, i.e., supposedly to the “right” of thetrue midpoint, in right brain damaged patients (RBD) whentheyarerequiredtosetwithoutcalculationthemidpointof3-,5-, 7- and 9-unit number intervals (e.g., “what is the midwaybetween 1 and 5?”; Zorzi et al., 2002; Rossetti et al., 2004;Doricchi et al., 2005a). The longer the interval the higher thebias and for very short 3-unit intervals the bias can showa paradoxical directional reversal toward numbers that aresmaller than the true midpoint (i.e., “cross-over” effect; Zorziet al., 2002; Doricchi et al., 2009). Based on the presence ofnumber interval bisection biases in RBD patients with leftspatial neglect and on the phenomenological similaritybetween these biases and biases usually displayed by neglectpatients in the bisection of long and short visual horizontallines (Doricchi et al., 2005b), it was proposed that numericalbiases are due to the extension of visual spatial neglect to theMNL (Zorzi et al., 2002), i.e., to neglect for smaller numberslocated on the left side of the MNL. This interpretationhowever, was not supported by several investigationsshowing that in RBD, neglect-like symptoms in mental-number space are not correlated to the severity or even thepresence of left spatial neglect in the bisection of visual linesand, more generally, of neglect in visual or imagery space(Doricchi et al., 2005a, 2009; Rossetti et al., 2004, 2011;Loetscher and Brugger, 2009; Loetscher et al., 2010; van Dijcket al., 2011; Aiello et al., in press; Pia et al., in press).Here we have found that crucial insights on the role playedby the right hemisphere in the representation of numbermagnitudes and on the origin of number interval bisectionbiases in RBD, can be gathered by exploring the consistencyofthese biases not only as a function of the length of a numberinterval but also as a function of the decade to whicha number interval belongs and as a function of the positionoccupied by an interval of a given length within a decade. Wehave re-analysed data collected over years in a sample of 77RBDpatientsandasampleof31age-matchedhealthycontrols(C) taken from Doricchi et al. (2009). Twenty-six patients (Nþ)hadleftsideneglectinthelinebisectiontask(meanrightwarddeviation ¼þ15.8 mm; five trials, line length ¼ 200 mm; cut-off score ¼þ6.5 mm; Azouvi et al., 2002) whereas 51 patients(N ) showed no rightward bisection bias (meandeviation ¼þ.39 mm). Nþ and N patients had comparablestroke onset time [104.7 and 91.4 days, respectively;F (1,75) ¼ .12, p ¼ .7]. Nþ,N and C did not differ in age [63.1,59.8 and 63.5 years, respectively; F (2,105) ¼ 1.9, p ¼ .14].Detailed clinical, anatomical data and inclusion criteria forRBD are reported in Doricchi et al. (2005a), (2009) and Aielloet al. (in press).Patients and C mentally bisected 3-,5-,7- and 9-unit inter-vals belonging to the first three decades (Zorzi et al., 2002).Intervals occupied both equivalent positions across thedecades (e.g., 7-unit interval: 1e7, 11e17, 21e27) and differentpositions within each decade (e.g., 7-unit interval e firstdecade: 1e7, 2e8, 3e9; Doricchi et al., 2009). Intervals were

Facial and Bodily Emotion Recognition in Multiple Sclerosis: The Role of Alexithymia and Other Characteristics of the Disease

Multiple sclerosis (MS) may be associated with impaired perception of facial emotions. However, emotion recognition mediated by bodily postures has never been examined in these patients. Moreover, several studies have suggested a relation between emotion recognition impairments and alexithymia. This is in line with the idea that the ability to recognize emotions requires the individuals to be able to understand their own emotions. Despite a deficit in emotion recognition has been observed in MS patients, the association between impaired emotion recognition and alexithymia has received little attention. The aim of this study was, first, to investigate MS patients abilities to recognize emotions mediated by both facial and bodily expressions and, second, to examine whether any observed deficits in emotions recognition could be explained by the presence of alexithymia. Thirty patients with MS and 30 healthy matched controls performed experimental tasks assessing emotion discrimination and recognition of facial expressions and bodily postures. Moreover, they completed questionnaires evaluating alexithymia, depression, and fatigue. First, facial emotion recognition and, to a lesser extent, bodily emotion recognition can be impaired in MS patients. In particular, patients with higher disability showed an impairment in emotion recognition compared with patients with lower disability and controls. Second, their deficit in emotion recognition was not predicted by alexithymia. Instead, the diseases characteristics and the performance on some cognitive tasks significantly correlated with emotion recognition. Impaired facial emotion recognition is a cognitive signature of MS that is not dependent on alexithymia.

Weight gain after STN-DBS: The role of reward sensitivity and impulsivity

Weight gain has been reported after deep brain stimulation of the subthalamic nucleus (STN-DBS), a widely used treatment for Parkinsons disease (PD). This nucleus has been repeatedly found to be linked both to reward and to inhibitory control, two key aspects in the control of food intake. In this study, we assessed whether weight gain experienced by patients with PD after STN-DBS, might be due to an alteration of reward and inhibitory functions. Eighteen patients with PD were compared to eighteen healthy controls and tested three times: before surgery, in ON medication and after surgery, respectively five days after the implantation in ON medication/OFF stimulation and at least three months after surgery in ON medication/ON stimulation. All participants were assessed for depression (Beck Depression Inventory), anhedonia (Snaith-Hamilton Pleasure Scale) and impulsiveness (Barratt Impulsiveness Scale). They performed a battery of tests assessing food reward sensitivity (Liking, Wanting and Preference) and a food go/no-go task. Results showed that body weight significantly increased after STN-DBS. A few days after surgery, patients were slower and more impulsive in the go/no-go task, showed a higher preference for high calorie (HC) foods and rated foods as less tasty. Months after subthalamic stimulation, the performance on the go/no-go task improved while no differences were observed in reward sensitivity. Interestingly, weight gain resulted greater in patients with higher levels of attentional impulsiveness pre-surgery, higher wanting for low calorie (LC) foods and impulsivity in the go/no-go task in ON medication/ON stimulation. However, only wanting and attentional impulsivity significantly predicted weight change. Furthermore, weight gain resulted associated with the reduction of l-Dopa after surgery and diseases duration. In conclusion, our findings are consistent with the view that weight gain in PD after STN-DBS has a multifactorial nature, which reflects the complex functional organization of the STN.

Emotional reactions in moral decision-making are influenced by empathy and alexithymia

ABSTRACT The role of emotional processes in driving moral choices remains debated. In particular, diminished emotional processing and reduced empathy have been associated with unusual high rates of utilitarian responses in moral judgments while, to date, the effects of diminished emotional processing and empathy on moral decision-making have been only partially considered. In this study, we investigated the influence of empathy and alexithymia on behavior and emotional responses while participants performed a moral decision task. Self-report (valence and arousal ratings) and physiological (skin conductance and heart rate) measures were collected during the task. Results showed that empathy and alexithymia shaped emotional reactions to moral decisions but did not bias moral choices. The more empathic the participants, the more dilemmas were perceived as unpleasant and arousing, and the greater the increase in skin conductance. Conversely, alexithymia was characterized by a reduced physiological activation during moral decisions, but normal self-report ratings. Heart rate was not modulated by empathy or alexithymia. These results add new evidence to the field of moral decision showing that empathy and alexithymia modulate emotional reactions to moral decision.

Body weight and its association with impulsivity in middle and old age individuals

&NA; Impulsivity, conceptualized as impulsive personality trait, poor inhibitory control and enhanced reward sensitivity, has been strongly linked to obesity. In particular, a disequilibrium between cognitive control and reward sensitivity has been observed in obese individuals in both behavioural and imaging studies. While this issue has been widely investigated in children and adults, it has received little attention in older adults. Here, obese and non‐obese participants aged between 40 and 70 years completed the Barratt Impulsiveness scale (assessing motor, non‐planning and attentional impulsiveness), a Go/no‐go task with foods and non‐foods (assessing inhibitory control) and a reward sensitivity battery with high and low caloric foods (assessing liking, wanting, tastiness and frequency of consumption). We observed that participants with higher BMI reported increased wanting for high calorie foods, but did not show poorer inhibitory control. Interestingly, participants who scored lower on the MMSE reported to consume high calorie more than low calorie foods. Finally, those who presented low scores on non‐planning and motor impulsiveness subscales reported higher tastiness ratings for low calorie foods. These results show that increased reward sensitivity but not reduced inhibitory control may characterize higher BMI during aging. Importantly, they also highlight new findings concerning food preferences among older adults.

You stole my food! Eating alterations in frontotemporal dementia

ABSTRACT Patients with different types of dementia may exhibit pathological eating habits, including food fads, hyperphagia, or even ingestion of inanimate objects. Several findings reveal that such eating alterations are more common in patients with frontotemporal dementia (FTD) than other types of dementia. Moreover, eating alterations may differ between the two variants of the disease, namely the behavioral variant and semantic dementia (SD). In this review, we summarized evidences regarding four areas: eating and body weight alterations in FTD, the most common assessment methods, anatomical correlates of eating disorders, and finally, proposed underlying mechanisms. An increasing understanding of the factors that contribute to eating abnormalities may allow first, a better comprehension of the clinical features of the disease and second, shed light on the mechanism underlying eating behaviors in the normal population.