The effect of lateralized dynamic stimuli on unilateral spatial neglect following right hemisphere lesions

Patients with unilateral (left-sided) spatial neglect following right-hemisphere stroke were tested for the effects of visual stimulation on performance of a line-bisection task. As predicted from research on brain mechanisms of spatial orientation and attention, dynamic visual stimuli presented on the left side substantially reduced neglect in the task. In contrast, left sided static stimuli reduced neglect significantly less and dynamic stimuli presented in the center had no effect on neglect. Neglect patients with hemianopia did not show significantly less benefit of left-sided dynamic stimuli compared to neglect patients without hemianopia, suggesting that the effect of these stimuli was unconscious and automatic. The potential advantages of lateralized dynamic stimuli in the rehabilitation of neglect are discussed.     

Dissociating verbal and nonverbal conceptual processing in the human brain

Functional neuroimaging has highlighted a left-hemisphere conceptual system shared by verbal and nonverbal processing despite neuropsychological evidence that the ability to recognize verbal and nonverbal stimuli can doubly dissociate in patients with left- and right-hemisphere lesions, respectively. Previous attempts to control for perceptual differences between verbal and nonverbal stimuli in functional neuroimaging studies may have hidden differences arising at the conceptual level. Here we used a different approach and controlled for perceptual confounds by looking for amodal verbal and nonverbal conceptual activations that are common to both the visual and auditory modalities. In addition to the left-hemisphere conceptual system activated by all meaningful stimuli, we observed the left/right double dissociation in verbal and nonverbal conceptual processing, predicted by neuropsychological studies. Left middle and superior temporal regions were selectively more involved in comprehending words--heard or read--and the right midfusiform and right posterior middle temporal cortex were selectively more involved in making sense of environmental sounds and images. Thus, the neuroanatomical basis of a verbal/nonverbal conceptual processing dissociation is established.     

Pineal lesion produces bilateral visual and auditory inattention in the rat

Unilateral lesions in such brain regions as medial frontal cortex and superior colliculus produce polysensory neglect contralateral to the lesion. Since the pineal gland is an unpaired brain structure, both electrophysiologically and hormonally responsive to visual and auditory stimulation, it may modulate bilateral sensory attention mechanisms. Long-Evans male rats were given pineal or sham lesions and were tested behaviourally. Sensory assessment revealed that in comparison to sham animals rats with pineal lesion exhibited unilateral visual and auditory neglect to stimuli presented on either side of the body. Animals with pineal lesions were more likely than sham-lesioned animals to demonstrate visual allesthesis and, compared to sham-lesioned rats, showed extinction on the left side to bilateral simultaneous visual stimulation. This is the first report that midline neuroendocrine damage can produce bilateral sensory inattention.     

Caloric stimulation in neglect: evaluation of response as a function of neglect type.

Contralesional neglect may be induced by either unawareness of contralesional stimuli (attentional neglect, AN) or failure to act in contralesional space (intentional neglect, IN). We examined whether contralesional cold caloric stimulation differentially affects AN versus IN. Patients with left-sided neglect (n = 16) from right-hemisphere lesions performed target cancellation and line bisection tasks. Using a video-based apparatus that reverses the right and left side of stimuli, patients with abnormal cancellation performance were divided into those with AN and those with IN. The 5 subjects with normal cancellation performance but rightward bisection bias were also separated into 2 neglect groups. Subjects performed cancellation or bisection tasks before and immediately after irrigation of the left auditory canal with ice water. Caloric stimulation induced brisk rightward nystagmus in all subjects. Subjects with AN cancelled more left-sided targets after stimulation than those with IN (p = .02). Whereas caloric stimulation significantly shifted bisection error leftward for both IN and AN groups (p < .0001), AN patients exhibited a greater magnitude of shift than the IN patients. While the basis for differential performance remains undefined, the data indicate that caloric stimulation influences AN more than IN.     

Neglect and hemianopia superimposed

In patients with posterior-parietal brain damage it is often difficult to decide whether left-sided omissions in perimetry are due to primary visual loss or due to visual neglect. We investigated 11 patients with combined neglect/hemianopia and 11 patients with pure hemianopia using a visual search task with single or double stimulation conditions. The second stimulus was either the fixation point itself (like in perimetry) or a distractor appearing in the hemifield opposite to the target. The fixation point did not worsen left-sided perception, but its disappearance led to a bias of exploration towards the right side in neglect patients but not in pure hemianopics. A distractor in the intact hemifield worsened the performance to left-sided stimuli, that is, neglect patients behaved as if they were completely hemianopic, even in intact parts of the visual field (VF). Three of the neglect patients showed unconscious processing of the distractor in the left VF, suggesting that the visual field defect was produced by neglect mechanisms rather than primary visual loss. This visual search paradigm appears to be helpful in understanding of the nature of hemianopia versus neglect deficits in individual patients.     

Neglect and Hemianopia Superimposed

In patients with posterior-parietal brain damage it is often difficult to decide whether left-sided omissions in perimetry are due to primary visual loss or due to visual neglect. We investigated 11 patients with combined neglect/hemianopia and 11 patients with pure hemianopia using a visual search task with single or double stimulation conditions. The second stimulus was either the fixation point itself (like in perimetry) or a distractor appearing in the hemifield opposite to the target. The fixation point did not worsen left-sided perception, but its disappearance led to a bias of exploration towards the right side in neglect patients but not in pure hemianopics. A distractor in the intact hemifield worsened the performance to left-sided stimuli, that is, neglect patients behaved as if they were completely hemianopic, even in intact parts of the visual field (VF). Three of the neglect patients showed unconscious processing of the distractor in the left VF, suggesting that the visual field defect was produced by neglect mechanisms rather than primary visual loss. This visual search paradigm appears to be helpful in understanding of the nature of hemianopia versus neglect deficits in individual patients.     

Effects of same- and different-modality cues in a Posner task: extinction-type,spatial, and non-spatial deficits after right-hemispheric stroke

The response delay to left target stimuli preceded by right-side cues, first described by Posner et al. [J. Neurosci. 4 (1984) 1863-1874] appears to be a stable marker of right-parietal injury. However, only few studies compared patients' performance to age-matched controls. Furthermore, only few studies compared visual and auditory stimuli in this task. Therefore, two groups of right-hemisphere stroke patients, with and without left visual hemineglect, and a healthy control group were studied in three versions of Posner's paradigm. Visual or auditory target stimuli were presented to the subject's left or right, following a visual or auditory cue by 150 ms. The classical 'extinction-type' effect, an increase in missing responses for right visual cue/left visual target, was specifically observed in neglect patients. In the same condition, an 'extinction-type' response delay was present in patients with neglect and in those without neglect. No such delay occurred in any group when cues were auditory. Specifically in neglect patients, response times were generally longer for left than for right visual targets, regardless of cue side and of cue modality. Response times were generally prolonged in neglect patients regardless of target modality. This suggests that three components impair neglect patients' performance in this paradigm: a non-spatial, supramodal deficit, a global, neglect-type deficit of the contralesional hemi-field, and the extinction-type impairment. The latter two deficits appear to be most marked within the visual domain.     

Hemianopia, hemianesthesia, and spatial neglect: a study with evoked potentials.

We recorded somatosensory or visual evoked potentials (SEPs, VEPs) to stimuli contralateral and ipsilateral to the lesion in three right-brain-damaged patients with left spatial hemineglect and in three left-brain-damaged patients without evidence of neglect, as assessed by visual exploratory tasks. All patients had contralateral homonymous hemianopia or hemianesthesia. The three neglect patients showed normal SEPs or VEPs to stimuli delivered to the left half-field or to the left hand, without conscious perception and verbal report of the stimulation. By contrast, the three left-brain-damaged patients without neglect showed no recognizable cortical evoked response to contralateral visual or somatosensory stimuli. In all patients, the cortical evoked responses to ipsilateral stimulation were normal. In patients with spatial hemineglect, hemianopia and hemianesthesia may be manifestations of the neglect syndrome (visual and somatosensory hemi-inattention), rather than representing primary sensory deficit. Visual and somatosensory hemi-inattention may be due to defective access to the neural processes subserving conscious perception by information that has undergone early sensory processing.     

Dissociation between taste and tactile extinction on the tongue after right brain damage

In patients with right brain damage (RBD) or left brain damage (LBD) and healthy subjects, tactile and three basic gustatory stimuli (sour, salty, bitter) were applied to the left or right hemitongues or to both hemitongues simultaneously. Tactile stimuli were detected and localized by verbal report, whereas gustatory stimuli were identified by pointing to the corresponding name on cards bearing the names of the three tastes. In the tactile test, 9 of 18 RBD patients showed extinction of left hemitongue stimuli, whereas the remaining RBD patients, 9 LBD patients and 14 healthy subjects detected virtually all stimuli in all conditions. In the gustatory test, healthy subjects outperformed the two brain damaged groups which nevertheless responded well above chance and did not differ from one another. Unexpectedly, the nine RBD patients with left hemitongue tactile extinction showed no gustatory extinction, since performance did not differ significantly between the two hemitongues on both unilateral and bilateral stimulations. To account for these findings, some evidence suggests that the tongue representation is bilateral in both modalities, but predominantly ipsilateral in the gustatory modality and predominantly contralateral in the tactile modality. The RBD patients with left hemitongue tactile extinction were those with more marked symptoms of left-sided extinction in the visual and auditory modalities, making it likely that their brain damage was also responsible for left lingual tactile extinction. The absence of left gustatory extinction in those patients can be attributed to the predominant channelling of left hemitongue taste inputs into the intact left hemisphere.     

Influence of response modality on awareness of contralesional tactile stimuli in right brain damaged patients

Thirty right brain-damaged (RBD) patients with left tactile extinction (19 of whom also showed neglect) were given a sequence of 240 tactile stimuli – 80 right, 80 left, 80 bilateral – across 4 different response conditions: (a) verbal report of stimulated side/s, (b) motor report of stimulated side/s, (c) verbal report of unstimulated side/s, (d) motor report of unstimulated side/s. Earlier experiments based on similar tasks but involving RBD patients with visual extinction and/or neglect have shown that visual awareness of contralesional stimuli can be influenced by manipulation of response conditions.

Since neglect and extinction can be double-dissociated both anatomically and behaviourally, the question arises of whether the underlying neuronal mechanisms are different. To answer this question the present work investigated the role of perceptual and premotor factors in generating tactile extinction in response to Double Simultaneous Stimulation (DSS). The hypothesis was that a directional response bias would result in an overall higher frequency of errors for verbal or motor responses indicating the ipsilesional side (right); a perceptual bias would instead result in errors distributed with similar frequency on the ipsilesional and the contralesional (left) side.

Results showed that, in RBD patients, contralesional extinction was not influenced by response conditions (verbal/motor; report of stimulated/unstimulated side) and presence/absence of neglect. This suggests that: (1) among RBD patients, directional response biases are unlikely to play a role in extinction of tactile stimuli on DSS; (2) the mechanisms underlying extinction are, at least to some extent, different from those underlying unilateral neglect.     

Sensory Symptoms and Processing of Nonverbal Auditory and Visual Stimuli in Children with Autism Spectrum Disorder

Atypical sensory responses are common in autism spectrum disorder (ASD). While evidence suggests impaired auditory–visual integration for verbal information, findings for nonverbal stimuli are inconsistent. We tested for sensory symptoms in children with ASD (using the Adolescent/Adult Sensory Profile) and examined unisensory and bisensory processing with a nonverbal auditory–visual paradigm, for which neurotypical adults show bisensory facilitation. ASD participants reported more atypical sensory symptoms overall, most prominently in the auditory modality. On the experimental task, reduced response times for bisensory compared to unisensory trials were seen in both ASD and control groups, but neither group showed significant race model violation (evidence of intermodal integration). Findings do not support impaired bisensory processing for simple nonverbal stimuli in high-functioning children with ASD.     

Evidence for asymmetric frontal-lobe involvement in episodic memory from functional magnetic resonance imaging and patients with unilateral frontal-lobe excisions

Recently, there has been considerable debate regarding the involvement of the left and right prefrontal cortices in the encoding and retrieval of episodic memory. In a previous PET study, we found that the use of easily verbalisable material may lead to activation predominantly in the left lateral frontal cortex whilst the use of non-easily verbalisable material may lead to activation predominantly in the right lateral frontal cortex, in both cases irrespective of encoding and retrieval processes. In order to replicate and extend these findings, the same task was modified for use with fMRI. Six healthy volunteers were scanned while encoding and then recalling stimuli that either emphasised visual or verbal processes. It was found that, in comparison to a baseline condition, the encoding of visual stimuli led to a bilateral activation of the prefrontal cortex whilst the encoding of verbal stimuli led to a preferential activation of the left prefrontal cortex. An effect of stimulus type was less evident during retrieval, with both visual and verbal stimuli leading to bilateral prefrontal cortex activation. Overall, encoding and retrieval activated similar regions of the prefrontal cortex suggesting that these areas mediate processes that are fundamental to both aspects of memory. To extend these findings further, the tasks used in the fMRI study were used to assess a group of patients with unilateral frontal lesions and a group of healthy control volunteers. The patients were significantly impaired compared to the healthy volunteers, although no significant differences were found in performance between the right- and left-sided lesioned patients. This result suggests that the memory-related asymmetries observed during functional neuroimaging studies may not be critical for task performance.     

Visual information processing in the left and right hemispheres

The effect of verbal vs nonverbal center fixation stimuli on visual half-field (VHF) asymmetry was investigated using both verbal and nonverbal VHF stimuli. Twenty adult subjects were administered word, face, and random shape VHF stimuli under both unilateral and bilateral viewing conditions.The results showed that VHF asymmetry was determined primarily by type of VHF stimuli under all viewing conditions. Words were recognized more often from the right VHF, faces were recognized more often from the left VHF, and random shapes showed no significant VHF difference. The results indicate that VHF asymmetry reflects differences in information processing capacity between the left and right hemispheres.     

Hypoperfusion of the auditory and prefrontal cortices in Parkinsonian patients with verbal hallucinations.

We examined patients with and without auditory hallucinations, using n-isopropyl-p-[123I]iodoamphetamine single photon emission computed tomographic imaging. We assessed verbal hallucinations in the present study: patients with nonverbal auditory hallucinations were excluded. A total of 11 patients with verbal and visual hallucinations and 17 patients with visual hallucinations only were enrolled. Patients with both verbal and visual hallucinations revealed significant hypoperfusion in the bilateral prefrontal cortex and right superior temporal gyrus compared to patients with visual hallucinations only. There were no significant hyperperfusion in patients with verbal plus visual hallucinations. These results may support the release hallucination theory in verbal hallucinations of Parkinson's disease, although another explanations may be more appropriate and further studies are required.     

Evidence for rapid auditory perception as the foundation of speech processing: a sparse temporal sampling fMRI study

We examined the processing of verbal and nonverbal auditory stimuli using an event-related functional magnetic resonance imaging (fMRI) study to reveal the neural underpinnings of rapid temporal information processing and it's relevance during speech perception. In the context of a clustered sparse-temporal fMRI data collection eight right-handed native German speakers performed: (i) an auditory gap detection task; and (ii) a CV syllable discrimination task. A tone perception task served as a nontemporal control condition. Here we aimed to research to what extent the left hemisphere preferentially processes linguistically relevant temporal information available in speech and nonspeech stimuli. Furthermore, we sought to find out as to whether a left hemisphere's preference for linguistically relevant temporal information is specifically constrained to verbal utterances or if nonlinguistic temporal information may also activate these areas. We collected haemodynamic responses from three time points of acquisition (TPA) with varying temporal distance from stimulus onset to gain an insight on the time course of auditory processing. Results show exclusively left-sided activations of primary and secondary auditory cortex associated with the perception of rapid temporal information. Furthermore, the data shows an overlap of activations evoked by nonspeech sounds and speech stimuli within primary and secondary auditory cortex of the left hemisphere. The present data clearly support the assumption of a shared neural network for rapid temporal information processing within the auditory domain for both speech and nonspeech signals situated in left superior temporal areas.     

Caloric stimulation and unilateral visual neglect

We studied performance on tests of visual neglect and left lateral gaze after caloric stimulation in 18 patients with left-sided visual neglect after strokes. Except for one patient with absent vestibulo-ocular responses, all improved during caloric stimulation on the left by cold (LC) or on the right by warm water (RW). Improvement seemed to depend on the facilitation of left lateral gaze and on past-pointing to the left. During LC and RW caloric stimulation, patients worked from left to right instead of their usual right to left. Caloric stimulation may be of use in training patients with hemispatial neglect to orient toward the affected hemispatial field.     

Effects of emotional prosody on auditory extinction for voices in patients with spatial neglect

The response of attention systems to emotional stimuli has been intensively investigated in the visual modality. Several findings suggest that neural mechanisms influencing selective attention towards emotional stimuli involve brain systems that are partly independent of cortical networks associated with the control of voluntary attention. To test this hypothesis in the auditory modality, we used a dichotic-listening paradigm in six right-hemisphere patients with left spatial neglect syndrome and left ear extinction during bilateral auditory stimulation. Three different meaningless emotional prosodic utterances (anger, fear, and happiness) were presented to the right or left ear, either alone or paired with another neutral utterance on the other side. Results showed fewer misses for emotional relative to neutral stimuli presented to the left ear, for all emotion categories, including happiness. In addition, we also examined the correlation between the site of brain lesions and the performance of patients for reporting left-ear stimuli. This exploratory anatomical analysis suggested that the relative advantage for emotional over neutral voices may be modulated by the site and extent of brain damage. This modulation consists of reduced influences of emotional prosody in patients with lesions in right ventral prefrontal lobe or right superior temporal cortex. Taken together, our results have provided new evidence that emotional attention mechanisms may be triggered in the auditory modality by negative and positive vocal stimuli.     

Unilateral visual neglect overcome by cues implicit in stimulus arrays.

The case of a man with a right hemisphere lesion and with evidence of left-sided visuospatial neglect is reported. On a variety of verbal and nonverbal tasks his performance was significantly modified by information implicit in stimulus configurations. Neglect deficits were present on tests involving spatially distinct or meaningless stimulus arrays but almost absent when stimuli were continuous or meaningfully integrated.     

Parallel interhemispheric processing in hemineglect: Relation to visual field defects

Parallel interhemispheric processing is required to explore our visual environment and to integrate visual information from both hemifields simultaneously. Damage to the right temporo-parietal cortex can disrupt such parallel processes and result in neglect and visual extinction of stimuli in the left contralesional visual space. Neglected or extinguished stimuli can still be processed, yet without reaching the patient's awareness. Such unconscious processing has been attributed to structurally intact primary visual areas in neglect. To study whether unconscious parallel processing depends on visual functional integrity, we compared the performance of neglect patients with visual field defects (VFDs) (n = 11) and hemianopic patients with partial or complete blindness of one visual hemifield (n = 11) on redundant targets effects (RTE). The RTE manifests as faster reaction times to redundant paired (two stimuli, one in each hemifield) than single stimulation (in one hemifield). We found RTEs, i.e., unconscious processing, in neglect patients but not in hemianopic patients. Furthermore, neglect patients showed large crossed–uncrossed differences (CUDs), i.e., faster response times to ipsi- than contralesional hemifield stimulation, reflecting a difference in processing speed for single stimuli in the two hemispheres that were correlated with VFDs and visual extinction. The finding that extinction, but not RTE, was correlated with the CUD suggests that under competitive bilateral stimulus conditions the delayed contralesional visual field input may not be detected by the intact left hemisphere, which presumably mediates the task given the impairment of the right hemisphere. By contrast, unconscious parallel processing of contralesional stimuli (RTE) occurred even when contralesional visual field input is lacking (VFD) or delayed (CUD) and is possibly mediated via subcortical visual pathways.     

Association between auditory and visual symptoms of unilateral spatial neglect

Unilateral spatial neglect due to right brain damage (RBD) can occur in several different sensory modalities in the same patient. Previous studies of the association between auditory and visual neglect have yielded conflicting outcomes. Most such studies have compared performance on relatively simple clinical measures of visual neglect, such as target cancellation, with that on more sophisticated measures of auditory perception. This is problematic because such tasks are typically not matched for the cognitive processes they exercise. We overcame this limitation by using equivalent visual and auditory versions of extinction and temporal-order judgment (TOJ) tasks. RBD patients demonstrated lateralized deficits on both visual and auditory tasks when compared with same-aged, healthy controls. Critically, a significant association between the severity of visual and auditory deficits was apparent on the TOJ task but not the extinction task, suggesting that even when task demands are matched across modalities, dissociations between visual and auditory neglect can be apparent. Across the auditory tasks, patients showed more pronounced deficits for verbal stimuli than for non-verbal stimuli. These findings have implications for recent models proposed to explain the role of spatial attention in multimodal perception.