Synesthesia & autistic features in a large family: Evidence for spatial imagery as a common factor.

BACKGROUND: Autism and synesthesia are neurodevelopmental conditions associated with variants of perceptual processing. They also share some genetic variants and include a large magnitude of intra-categorical variation: 60 types for synesthesia, as well as a spectrum for autism. In order to investigate the relationship between these two phenomena, we investigated the family of FC, an autistic individual who also possess savant abilities and synesthesia manifestations. METHOD: Autistic symptoms were assessed for the entire sample of participants entering the study (39 individuals) using the SRS. Participants above threshold were evaluated with standardized diagnostic tools. Synesthesia was explored in the entire participating sample using a self-reported questionnaire. Consistency tests were used for participants who reported synesthetic manifestations. RESULTS: In addition to FC, four individuals with ASD were detected. Fifteen participants self-reported synesthesia (15 sequence-space, 4 sound-shape, 4 day-color), among which nine sequence-space synesthetes satisfied the consistency criteria. Two participants possess both autism and synesthesia. CONCLUSION: This family illustrates the co-segregation of autism and synesthesia. This co-segregation is in favour of a partially overlapping genetic predisposition for both conditions, but also authorizes a large variety of manifestations in both conditions. The high prevalence of sequence-space synesthesia in this family strengthens the previous assumption that this form of synesthesia may be linked to autism. We discuss the potential role of spatial imagery in the development of this form of synesthesia and savant abilities.

[Treatment of neglect: new therapy approaches]. / Neglektbehandlung: neue Therapieansätze.

Neglect is a supramodal, clinically relevant disorder, which occurs in the different sensory modalities as well as in the mental representation. The different manifestations of neglect show interindividual and intraindividual variation. Different spatial and attention-related interventions lead to varying degrees of improvement in neglect symptoms but are often not stable in time or transferable to activities of daily living. Representational deficits or body-related aspects to modify personal neglect are rarely a priority in current therapies. Because of the multisensory and motor deficits from our point of view the future of neglect rehabilitation lies in a combined therapy of visual exploration, motor imagery with intensive motor therapy of motor sensory deficits and probably best reinforced by continued neck muscle vibration or allocation of attention to the neglected side.

Exogenous orienting of attention in hearing: a virtual reality paradigm to assess auditory attention in neglect patients.

While mechanisms of orienting attention in unilateral spatial neglect (USN) have frequently been studied in the visual domain, these mechanisms remain relatively unexplored in the auditory domain. Our first goal was to replicate Spence and Driver's (J Exp Psychol Hum 22:1005-1030, 1994) results with a virtual reality paradigm. This paradigm simulated a 3-dimensional auditory space with headphones. Our second aim was to study auditory profiles of orienting attention in USN. In a first experiment, 18 healthy participants performed an auditory cueing spatial paradigm (either a target-detection task or a target-lateralization task). In a second experiment, 14 right-stroke patients (10 with USN and 4 without USN) performed these two same tasks. As in Spence and Driver's (J Exp Psychol Hum 22:1005-1030, 1994), our first experiment showed that spatial representations are not utilized for the detection of auditory stimuli. However, during the lateralization task, participants were quicker to detect targets preceded by a spatially congruent cue, which suggests that our paradigm could be suitable for studying orienting attention in hearing. Our second experiment found that patients with USN also needed an explicit spatial task to be sensitive to auditory spatial cueing. In the target-lateralization task, they showed effects lateralized only to one side of space, whereas patients without USN did not. Although our paradigm needs replications to better understand orienting attention impairments in hearing in USN, this study could have implications for the development of clinical tasks that could assess auditory spatial attention in USN syndrome.

Spontaneous ocular positioning during visual imagery in patients with hemianopia and/or hemineglect.

Spontaneous eye movements during imagery are not random and can be used to study and reveal mental visualization processes (Fourtassi et al., 2013; Johansson et al. 2006). For example, we previously showed that during memory recall of French towns via imagery healthy individuals looks straight ahead when recalling Paris and their subsequent gaze positions are significantly correlated with the real GPS coordinates of the recalled towns. This correlation suggests that memory retrieval is done via depictive representations as it is never found when the towns are recalled using verbal fluency. In the present paper we added to this finding by showing that the mental image is spontaneously centered on the head or body midline. In order to investigate the capacities of visual imagery in patients, and by extension, the role of primary visual cortex and fronto-parietal cortex in spatial visual imagery, we recorded gaze positions during memory recall of French towns in an imagery task, a non-imagery task (verbal fluency), and a visually-guided task in five patients with left or right hemianopia and in four patients with hemineglect (two with left hemianopia and two without). The correlation between gaze position and real GPS coordinates of the recalled towns was significant in all hemianopic patients, but in patients with hemineglect this was only the case for towns located on the right half of the map of France. This suggests hemianopic patients can perform spatially consistent mental imagery despite direct or indirect unilateral lesions of the primary visual cortex. In contrast, the left-sided towns recalled by hemineglect patients, revealed that they have some spatial inconsistency or representational difficulty. Hemianopic patients positioned and maintained their gaze in their contralesional hemispace, suggesting that their mental map was not centered on their head or body midline. This contralesional gaze positioning appeared to be a general compensation strategy and was not observed in patients with neglect (with or without hemianopia). Instead, neglect patients positioned their gaze in their ipsilesional hemispace and only when performing the visual imagery task. These findings are discussed in the context of the role of occipital and fronto-parietal cortices in the neuroanatomical model of visual imagery developed by Kosslyn et al. (2006).

Auditory lateralisation deficits in neglect patients.

Although visual deficits due to unilateral spatial neglect (USN) have been frequently described in the literature, fewer studies have been interested in directional hearing impairment in USN. The aim of this study was to explore sound lateralisation deficits in USN. Using a paradigm inspired by Tanaka et al. (1999), interaural time differences (ITD) were presented over headphones to give the illusion of a leftward or a rightward movement of sound. Participants were asked to respond "right" and "left" as soon as possible to indicate whether they heard the sound moving to the right or to the left side of the auditory space. We additionally adopted a single-case method to analyse the performance of 15 patients with right-hemisphere (RH) stroke and added two additional measures to underline sound lateralisation on the left side and on the right side. We included 15 patients with RH stoke (5 with a severe USN, 5 with a mild USN and 5 without USN) and 11 healthy age-matched participants. We expected to replicate findings of abnormal sound lateralisation in USN. However, although a sound lateralisation deficit was observed in USN, two different deficit profiles were identified. Namely, patients with a severe USN seemed to have left sound lateralisation impairment whereas patients with a mild USN seemed to be more influenced by a systematic bias in auditory representation with respect to body meridian axis (egocentric deviation). This latter profile was unexpected as sounds were manipulated with ITD and, thus, would not be perceived as coming from an external source of the head. Future studies should use this paradigm in order to better understand these two distinct profiles.

Clock desynchronisation: why and how?

The internal clock located in the suprachiasmatic nuclei of the anterior hypothalamus is controlled by external (environment and social life) and genetic factors. Desynchronisation of the organism occurs when the clock does no longer work in harmony with the environ- mentalfactors. Rhythm desynchronization can be related to a conflict between the clock and environmentalfactors (shift work, night shift, transmeridianflight), to inefficient synchro- nizers (aging, psychiatric diseases..), to badly received synchronizers (circadian rhythm sleep disorders with e.g delayed or advanced sleep phase syndromes), or to the use of some drugs (lithium, propofol, alcohol...). In the long term rhythm desynchronisation can result in serious illnesses and the use of resynchronizing agents like melatonin or bright light are useful to the clock resynchronization.

Anosognosia and neglect respond differently to the same treatments.

Different techniques, such as optokinetic stimulation, adaptation to prismatic shift of the visual field to the right, or transcutaneous electrical nerve stimulation (TENS), have been shown to alleviate neglect, at least temporarily. We assessed the effect of these techniques on anosognosia and whether their therapeutic effect, if any, matches that on neglect. The effect of the three types of treatment on anosognosia and neglect was investigated in five patients presenting with both severe anosognosia and neglect. Patient 1 was treatment responsive to anosognosia but not to neglect, whereas patients 4 and 5 showed the reverse pattern, i.e., they were treatment responsive to neglect but not to anosognosia. This "treatment response bias" proved to be a valid means to investigate different effects of treatments in the same patient.

Cognitive maps in imagery neglect.

Patients with imagery neglect (RI+) show peculiar difficulties in orienting themselves in the environment. Navigational impairments could be due to a deficit in creating or using a mental representation of the environment (Guariglia, Piccardi, Iaria, Nico, & Pizzamiglio, 2005) or, according to the BBB model (Burgess, Becker, King, & O'Keefe, 2001), to a specific deficit in a mechanism that transforms an allocentric representation into an egocentric one and vice versa. Previous studies, however, do not allow discerning between a deficit in forming or in using a cognitive map, taking no notice of the fact that these are two different abilities underlain by different neuroanatomical areas, which could be independently impaired. Furthermore, the BBB model has never been verified in a population of brain-damaged patients. Therefore, we administered two tasks that separately assess the ability to create and use a cognitive map of the environment to 28 right brain-damaged patients (4 patients with imagery neglect and 4 patients with perceptual neglect) and 11 healthy participants. RI+ patients showed no specific deficit in creating or using a cognitive map, but failed to transform an egocentric representation of the environment into an allocentric one and vice versa, as predicted by the BBB model.

Representational neglect for words as revealed by bisection tasks.

In the present study, we showed that a representational disorder for words can dissociate from both representational neglect for objects and neglect dyslexia. This study involved 14 brain-damaged patients with left unilateral spatial neglect and a group of normal subjects. Patients were divided into four groups based on presence of left neglect dyslexia and representational neglect for non-verbal material, as evaluated by the Clock Drawing test. The patients were presented with bisection tasks for words and lines. The word bisection tasks (with words of five and seven letters) comprised the following: (1) representational bisection: the experimenter pronounced a word and then asked the patient to name the letter in the middle position; (2) visual bisection: same as (1) with stimuli presented visually; and (3) motor bisection: the patient was asked to cross out the letter in the middle position. The standard line bisection task was presented using lines of different length. Consistent with the literature, long lines were bisected to the right and short lines, rendered comparable in length to the words of the word bisection test, deviated to the left (crossover effect). Both patients and controls showed the same leftward bias on words in the visual and motor bisection conditions. A significant difference emerged between the groups only in the case of the representational bisection task, whereas the group exhibiting neglect dyslexia associated with representational neglect for objects showed a significant rightward bias, while the other three patient groups and the controls showed a leftward bisection bias. Neither the presence of neglect alone nor the presence of visual neglect dyslexia was sufficient to produce a specific disorder in mental imagery. These results demonstrate a specific representational neglect for words independent of both representational neglect and neglect dyslexia.

Sensory processing dysfunctions as expressed among children with different severities of intellectual developmental disabilities.

High frequency of sensory processing dysfunctions (SPD) is prevalent among children with intellectual developmental disabilities and contributes to their maladaptive behaviors. However, the knowledge about the expressions of SPD in different levels of IDD severity is limited. As SPD may reduce adaptive responses and limit participation, this knowledge should be elaborated. The purpose of the present study was to examine the specific expressions of sensory processing among children with different severity levels of IDD. Participants were 91 children aged 4-9 years with mild, moderate severe-profound and IDD. Their parents completed the short sensory profile (SSP). According the results, SPD were manifested across all levels of IDD. Groups differed in specific behaviors related to sensory stimuli. The highest percentage of children with severe sensory processing difficulties was found among children with mild and sever IDD level. SPD may characterize children with all severity levels of IDD. Nevertheless, the probability that children with a specific IDD level will be more vulnerable to specific aspects of SPD emphasizes the need for early evaluation and intervention to address the specific sensory needs of children with different IDD levels. This may enhance their development, performance and participation in daily living.

Attention deficits following ADEM ameliorated by guanfacine.

The authors report here the case of a patient with severe deficits in arousal and sustained attention, associated with hemispatial neglect. These impairments were secondary to acute disseminated encephalomyelitis, with bilateral involvement of the medial nuclei and pulvinar of the thalamus. Treatment with the noradrenergic agonist guanfacine, previously used for attention deficits in attention deficit/hyperactivity disorder and stroke, was associated with a significant amelioration of both the spatial and sustained attention impairments in neglect. Guanfacine may prove to be a useful tool in the treatment of disorders of attention associated with neurological conditions.

Auditory and cognitive deficits associated with acquired amusia after stroke: a magnetoencephalography and neuropsychological follow-up study.

Acquired amusia is a common disorder after damage to the middle cerebral artery (MCA) territory. However, its neurocognitive mechanisms, especially the relative contribution of perceptual and cognitive factors, are still unclear. We studied cognitive and auditory processing in the amusic brain by performing neuropsychological testing as well as magnetoencephalography (MEG) measurements of frequency and duration discrimination using magnetic mismatch negativity (MMNm) recordings. Fifty-three patients with a left (n = 24) or right (n = 29) hemisphere MCA stroke (MRI verified) were investigated 1 week, 3 months, and 6 months after the stroke. Amusia was evaluated using the Montreal Battery of Evaluation of Amusia (MBEA). We found that amusia caused by right hemisphere damage (RHD), especially to temporal and frontal areas, was more severe than amusia caused by left hemisphere damage (LHD). Furthermore, the severity of amusia was found to correlate with weaker frequency MMNm responses only in amusic RHD patients. Additionally, within the RHD subgroup, the amusic patients who had damage to the auditory cortex (AC) showed worse recovery on the MBEA as well as weaker MMNm responses throughout the 6-month follow-up than the non-amusic patients or the amusic patients without AC damage. Furthermore, the amusic patients both with and without AC damage performed worse than the non-amusic patients on tests of working memory, attention, and cognitive flexibility. These findings suggest domain-general cognitive deficits to be the primary mechanism underlying amusia without AC damage whereas amusia with AC damage is associated with both auditory and cognitive deficits.

Does hemineglect affect visual mental imagery? Imagery deficits in representational and perceptual neglect.

To give new insight about the relationship between imagery processes and different types of hemispatial neglect, we assessed different mental imagery abilities in a sample of right- and left-brain-damaged patients. Furthermore, because of reports of a mental representation disorder for environments in patients affected by representational neglect we also tested their navigational imagery ability. We found that patients with no signs of perceptual or representational neglect performed flawlessly on our imagery tasks regardless of whether they had left- or right-sided lesions. By contrast, patients affected by neglect failed most of the tests; in particular, representational neglect patients failed one test of mental transformation and tests requiring the manipulation of cognitive maps. These results suggest there is a specific relationship between hemispatial neglect and deficits in visual mental imagery and demonstrate that the right hemisphere plays a specific role in visual mental imagery.

Environment and object mental images in patients with representational neglect: two case reports.

The aim of this study was to shed light on the nature of the imagery deficits in two patients with representational neglect and to determine whether representational neglect is affected by the content of the mental images the patients have to generate, inspect and manipulate. In particular, we submitted two patients with different types of representational neglect to a battery of visual mental imagery tests to assess the different kinds of imagery processes. We found that Patient 1, whose performance was asymmetrical on the O'Clock Test, performed poorly on tasks involving the mental generation, inspection and manipulation of objects but showed no deficit on tasks involving the mental generation, inspection and manipulation of environments. On the other hand, Patient 2, whose performance was asymmetrical on the Familiar Squares Description Test, performed poorly on tasks involving the mental generation, inspection and manipulation of environments, but not on tasks involving the mental generation, inspection and manipulation of objects. Our results demonstrate that environments and objects in the imagery domain can be represented separately and can be selectively affected by damage following brain lesions.

Wheel-chair driving improvement following visuo-manual prism adaptation.

Prism adaptation has been used for several years to improve several aspects of unilateral neglect. Parameters ranging from the classical neuropsychological tests to mental imagery or to tactile extinction have been successfully ameliorated following a brief period of adaptation to wedge prisms shifting the visual field to the right. However the potential therapeutic implications of this technique depend on the investigation of more functional and ecological parameters. Here we describe a patient with left hemiplegia and unilateral neglect who was impaired during wheel-chair navigation in the clinical unit. Following a brief adaptation period, this patient showed a sudden improvement of wheel-chair driving as well as of classical tests. The potential implications of prism adaptation for the rehabilitation of unilateral neglect are highlighted by the long duration of improvement obtained after a single adaptation session.

Synaesthesia for reading and playing musical notes.

This study reports three cases of synaesthesia who experience colors in response to written musical notation, graphemes and heard music. The synaesthetes show Stroop-like interference when asked to name the colour of graphemes but not for written musical notes. However, reliable interference is found in two further studies that require deeper processing of the musical notation (namely playing music from colored notation, and naming the synaesthetic color of the notes whilst suppressing the veridical color). This is the first empirical demonstration of synaesthesia for musical notation. The fact that synaesthetic color influences music playing/reading (a sensory-motor transformation) but not verbal color naming suggests that synaesthetic Stroop effects can arise from processing the meaning of a stimulus and not just as a result of verbal response interference. However, it is likely that the color associations themselves have a developmental origin in the names assigned to them. In all three cases, the colors of the written notes are related to the graphemes that arbitrarily denote them (e.g., 'A' may be "red" both as a letter and when written in musical notation). The results suggest that synaesthetic associations may migrate from one representational format (e.g., graphemes) to another (e.g., musical notation).

Prepulse facilitation and prepulse inhibition in schizophrenia patients and their unaffected siblings.

BACKGROUND: Deficits in schizophrenia patients and their first-degree relatives have been reported in prepulse inhibition (PPI), a phenomenon that measures an early stage of information processing (sensorimotor gating). It is less clear whether these information processing deficits extend to prepulse facilitation (PPF), which measures a later stage of generalized alerting or orienting. METHODS: This study examined three separate issues: first, whether schizophrenia patients have deficits in PPI and PPF; second, whether the siblings of patients show deficits in these processes; and third, whether prepulse duration influences the degree of the deficits. These issues were examined in 76 schizophrenia patients, 36 of their siblings, and 41 normal control subjects. RESULTS: Patients and siblings did not differ from control subjects in PPI, perhaps due to the use of different procedural parameters compared with other laboratories that have consistently found PPI deficits in schizophrenia patients. Patients and their siblings produced significantly less PPF than control subjects. For both PPI and PPF, prepulse duration was not a significant factor. CONCLUSIONS: These results imply that PPF deficits reveal a generalized alerting or orienting deficit that is present in both schizophrenia patients and their siblings, suggesting that this deficit may be tapping an endophenotypic vulnerability factor.

Between language and space: a cross-domain interaction.

We document for the first time the effect of a spatial deficit on an spoken language task. Right brain-damaged patients with and without neglect were administered a task of emphatic stress. Patients listened to 60 subject-verb-object sentence pairs. The emphatic stress could be placed on the subject, on the verb or on the object word. Patients had to judge whether the two sentences were same or different for the position of the emphatic stress. The judgements were more impaired in patients with neglect and when the stress was placed at the beginning of the sentence (on the subject word), that is to say, at the leftmost location of a hypothetical spatial representation of the heard sentence. We hypothesize that auditory language undergoes a spatial transcoding, and that this transcoding is affected by the presence of a spatial bias like that observed in patients with neglect.

Limb activation effects in hemispatial neglect.

OBJECTIVE: To assess the efficacy of passive and active limb movement to improve visual scanning in patients with hemispatial neglect. DESIGN: Before-after trial: behavioral analyses of a case series. SETTING: Stroke rehabilitation unit in a tertiary care hospital. PARTICIPANTS: Nine individuals with right-hemisphere stroke (mean time poststroke, 19.5 mo) and left-sided neglect, as assessed by the Sunnybrook Bedside Neglect Battery. INTERVENTION: Active left limb movement (button push; n=3) or passive left limb movement (n=8) with functional electric stimulation (FES) administered during visual scanning testing. MAIN OUTCOME MEASURES: Performance on visual scanning tests involving naming of letters and numbers. RESULTS: Both active and passive movement significantly improved target detection on the left side, but not on the right side, on the visual scanning task. Positive results were seen in 2 of 3 active movement patients and 6 of 8 passive movement patients. CONCLUSIONS: Both active and FES-stimulated passive movements are potential techniques for the treatment of hemispatial neglect.