Personalized connectome fingerprints: Their importance in cognition from childhood to adult years.

Structural neural network architecture patterns in the human brain could be related to individual differences in phenotype, behavior, genetic determinants, and clinical outcomes from neuropsychiatric disorders. Recent studies have indicated that a personalized neural (brain) fingerprint can be identified from structural brain connectomes. However, the accuracy, reproducibility and translational potential of personalized fingerprints in terms of cognition is not yet fully determined. In this study, we introduce a dynamic connectome modeling approach to identify a critical set of white matter subnetworks that can be used as a personalized fingerprint. Several individual variable assessments were performed that demonstrate the accuracy and practicality of personalized fingerprint, specifically predicting the identity and IQ of middle age adults, and the developmental quotient in toddlers. Our findings suggest the fingerprint found by our dynamic modeling approach is sufficient for differentiation between individuals, and is also capable of predicting general intellectual ability across human development.

Damage to left anterior temporal cortex predicts impairment of complex syntactic processing: a lesion-symptom mapping study.

Sentence processing problems form a common consequence of left-hemisphere brain injury, in some patients to such an extent that their pattern of language performance is characterized as "agrammatic". However, the location of left-hemisphere damage that causes such problems remains controversial. It has been suggested that the critical site for syntactic processing is Broca's area of the frontal cortex or, alternatively, that a more widely distributed network is responsible for syntactic processing. The aim of this study was to identify brain regions that are required for successful sentence processing. Voxel-based lesion-symptom mapping (VLSM) was used to identify brain regions where injury predicted impaired sentence processing in 50 native speakers of Icelandic with left-hemisphere stroke. Sentence processing was assessed by having individuals identify which picture corresponded to a verbally presented sentence. The VLSM analysis revealed that impaired sentence processing was best predicted by damage to a large left-hemisphere temporo-parieto-occipital area. This is likely due to the multimodal nature of the sentence processing task, which involves auditory and visual analysis, as well as lexical and syntactic processing. Specifically impaired processing of noncanonical sentence types, when compared with canonical sentence processing, was associated with damage to the left-hemisphere anterior superior and middle temporal gyri and the temporal pole. Anterior temporal cortex, therefore, appears to play a crucial role in syntactic processing, and patients with brain damage to this area are more likely to present with receptive agrammatism than patients in which anterior temporal cortex is spared.

Asymmetrical extra-hippocampal grey matter loss related to hippocampal atrophy in patients with medial temporal lobe epilepsy.

BACKGROUND: Structural neuroimaging studies have consistently shown a pattern of extra-hippocampal atrophy in patients with left and right drug-refractory medial temporal lobe epilepsy (MTLE). However, it is not yet completely understood how extra-hippocampal atrophy is related to hippocampal atrophy. Moreover, patients with left MTLE often exhibit more intense cognitive impairment, and subtle brain asymmetries have been reported in patients with left MTLE versus right MTLE but have not been explored in a controlled study. OBJECTIVES: To investigate the association between extra-hippocampal and hippocampal atrophy in patients with MTLE, and the effect of side of hippocampal atrophy on extra-hippocampal atrophy. METHODS: Voxel-based morphometry analyses of magnetic resonance images of the brain were performed to determine the correlation between regional extra-hippocampal grey matter volume and hippocampal grey matter volume. The results from 36 patients with right and left MTLE were compared, and results from the two groups were compared with those from 49 healthy controls. RESULTS: Compared with controls, patients with MTLE showed a more intense correlation between hippocampal grey matter volume and regional grey matter volume in locations such as the contralateral hippocampus, bilateral parahippocampal gyri and frontal and parietal areas. Compared with right MTLE, patients with left MTLE exhibited a wider area of atrophy related to hippocampal grey matter loss, encompassing both the contralateral and ipsilateral hemispheres, particularly affecting the contralateral hippocampus. CONCLUSIONS: Our results suggest that left hippocampal atrophy is associated with a larger degree of extra-hippocampal atrophy. This may help to explain the more intense cognitive impairment usually observed in these patients.

Group study of an "undercover" test for visuospatial neglect: invisible cancellation can reveal more neglect than standard cancellation.

Visual neglect is a relatively common deficit after brain damage, particularly strokes. Cancellation tests provide standard clinical measures of neglect severity and deficits in daily life. A recent single-case study introduced a new variation on standard cancellation. Instead of making a visible mark on each target found, the patient made invisible marks (recorded with carbon paper underneath, for later scoring). Such invisible cancellation was found to reveal more neglect than cancellation with visible marks. Here we test the generality of this. Twenty three successive cases with suspected neglect each performed cancellation with visible or invisible marks. Neglect of contralesional targets was more pronounced with invisible marks. Indeed, about half of the patients only showed neglect in this version. For cases showing more neglect with invisible marks, stronger neglect of contralesional targets correlated with more revisits to ipsilesional targets for making additional invisible marks upon them. These results indicate that cancellation with invisible marks can reveal more neglect than standard cancellation with visible marks, while still providing a practical bedside test. Our observations may be consistent with recent proposals that demands on spatial working memory (required to keep track of previously found items only when marked invisibly) can exacerbate spatial neglect.

Medial temporal lobe atrophy in patients with refractory temporal lobe epilepsy.

OBJECTIVE: The objective of this study was to assess the volumes of medial temporal lobe structures using high resolution magnetic resonance images from patients with chronic refractory medial temporal lobe epilepsy (MTLE). METHODS: We studied 30 healthy subjects, and 25 patients with drug refractory MTLE and unilateral hippocampal atrophy (HA). We used T1 magnetic resonance images with 1 mm isotropic voxels, and applied a field non-homogeneity correction and a linear stereotaxic transformation into a standard space. The structures of interest are the entorhinal cortex, perirhinal cortex, parahippocampal cortex, temporopolar cortex, hippocampus, and amygdala. Structures were identified by visual examination of the coronal, sagittal, and axial planes. The threshold of statistical significance was set to p<0.05. RESULTS: Patients with right and left MTLE showed a reduction in volume of the entorhinal (p<0.001) and perirhinal (p<0.01) cortices ipsilateral to the HA, compared with normal controls. Patients with right MTLE exhibited a significant asymmetry of all studied structures; the right hemisphere structures had smaller volume than their left side counterparts. We did not observe linear correlations between the volumes of different structures of the medial temporal lobe in patients with MTLE. CONCLUSION: Patients with refractory MTLE have damage in the temporal lobe that extends beyond the hippocampus, and affects the regions with close anatomical and functional connections to the hippocampus.

Cognitive control mechanisms revealed by ERP and fMRI: evidence from repeated task-switching.

We investigated the extent to which a common neural mechanism is involved in task set-switching and response withholding, factors that are frequently confounded in task-switching and go/no-go paradigms. Subjects' brain activity was measured using event-related electrical potentials (ERPs) and event-related functional MRI (fMRI) neuroimaging in separate studies using the same cognitive paradigm. Subjects made compatible left/right keypress responses to left/right arrow stimuli of 1000 msec duration; they switched every two trials between responding at stimulus onset (GO task-green arrows) and stimulus offset (WAIT task-red arrows). With-holding an immediate response (WAIT vs. GO) elicited an enhancement of the frontal N2 ERP and lateral PFC activation of the right hemisphere, both previously associated with the "no-go" response, but only on switch trials. Task-switching (switch vs. nonswitch) was associated with frontal N2 amplification and right hemisphere ventrolateral PFC activation, but only for the WAIT task. The anterior cingulate cortex (ACC) was the only brain region to be activated for both types of task switch, but this activation was located more rostrally for the WAIT than for the GO switch trials. We conclude that the frontal N2 ERP and lateral PFC activation are not markers for withholding an immediate response or switching tasks per se, but are associated with switching into a response-suppression mode. Different regions within the ACC may be involved in two processes integral to task-switching: processing response conflict (rostral ACC) and overcoming prior response suppression (caudal ACC).

The perception of body orientation after neck-proprioceptive stimulation. Effects of time and of visual cueing.

Different sensory systems (e.g. proprioception and vision) have a combined influence on the perception of body orientation, but the timescale over which they can be integrated remains unknown. Here we examined how visual information and neck proprioception interact in perception of the "subjective straight ahead" (SSA), as a function of time since initial stimulation. In complete darkness, healthy subjects directed a laser spot to the point felt subjectively to be exactly straight ahead of the trunk. As previously observed, left neck muscle vibration led to a disparity between subjective perception and objective position of the body midline, with SSA misplaced to the left. We found that this displacement was sustained throughout 28 min of continuous proprioceptive stimulation, provided there was no visual input. Moreover, prolonged vibration of neck muscles leads to a continuing disparity between subjective and objective body orientation even after offset of the vibration; the longer the preceding vibration, the more persistent the illusory deviation of body orientation. To examine the role of vision, one group of subjects fixated a central visual target at the start of each block of continuous neck vibration, with SSA then measured at successive intervals in darkness. The illusory deviation of SSA was eliminated whenever visual input was provided, but returned as a linear function of time when visual information was eliminated. These results reveal: the persistent effects of neck proprioception on the SSA, both during and after vibration; the influence of vision; and integration between incoming proprioceptive information and working memory traces of visual information.

Ipsilesional biases in saccades but not perception after lesions of the human inferior parietal lobule.

We examined the effects of chronic unilateral lesions to either the inferior parietal lobe, or to the dorsolateral prefrontal cortex including the frontal eye fields (FEFs), upon human visual perception and saccades in temporal-order-judgment (TOJ) tasks. Two visual events were presented on each trial, one in each hemifield at various stimulus onset asynchronies (SOAs). In the saccade task, patients moved their eyes to whichever stimulus attracted gaze first. In the perceptual-manual task, they pressed a button to indicate which stimulus was perceived first. Frontal patients showed appropriate TOJs for visual targets in both tasks. Parietal patients showed appropriate TOJs in the perceptual-manual but not the saccade task; their saccades tended to be ipsilesional unless the contralesional target led substantially. This reveals a bias in saccade choice after parietal damage that cannot be attributed to deficient visual perception. These results challenge previous claims that only anterior lesions produce motoric spatial biases in humans. However, they are in accord with recent neurophysiological evidence for parietal involvement in saccade generation, and also with suggestions that visuomotor transformations in the parietal lobe serving direct spatial motor responses can dissociate from conscious perception as indicated by indirect arbitrary responses.

Spatial normalization of brain images with focal lesions using cost function masking.

In studies of patients with focal brain lesions, it is often useful to coregister an image of the patient's brain to that of another subject or a standard template. We refer to this process as spatial normalization. Spatial normalization can improve the presentation and analysis of lesion location in neuropsychological studies; it can also allow other data, for example from functional imaging, to be compared to data from other patients or normal controls. In functional imaging, the standard procedure for spatial normalization is to use an automated algorithm, which minimizes a measure of difference between image and template, based on image intensity values. These algorithms usually optimize both linear (translations, rotations, zooms, and shears) and nonlinear transforms. In the presence of a focal lesion, automated algorithms attempt to reduce image mismatch between template and image at the site of the lesion. This can lead to significant inappropriate image distortion, especially when nonlinear transforms are used. One solution is to use cost-function masking-masking the areas used in the calculation of image difference-to exclude the area of the lesion, so that the lesion does not bias the transformations. We introduce and evaluate this technique using normalizations of a selection of brains with focal lesions and normal brains with simulated lesions. Our results suggest that cost-function masking is superior to the standard approach to this problem, which is affine-only normalization; we propose that cost-function masking should be used routinely for normalizations of brains with focal lesions.

Spatial deployment of attention within and across hemifields in an auditory task.

Research on visual attention has demonstrated that covert attention can be focused on particular locations within one hemifield, but that a specific "meridian" cost may also be found for shifting attention between hemifields. These issues have received less consideration for audition, even though reliable behavioral measures for the effects of spatial attention on hearing are now available. We examined the spatial distribution of covert attention in an auditory task following spatially non-predictive peripheral auditory cues (which should induce exogenous attention shifts), or following symbolic central cues that predicted the likely location for the auditory target (to induce endogenous attention shifts). In both cases, we found that attention can be focused not only on one hemifield versus another, but also within one hemifield in an auditory task. However, there was no unequivocal evidence for a meridian effect in audition.

Do neck-proprioceptive and caloric-vestibular stimulation influence covert visual attention in normals, as they influence visual neglect?

Neck-proprioceptive and caloric-vestibular stimulation have been shown to ameliorate the spatial bias exhibited by patients suffering from unilateral visual neglect. These interventions might in principle have their effect by biasing covert attention towards the neglected side. If so, the same interventions should also modulate covert attention in neurologically-intact subjects. However, we demonstrate here that neither neck-proprioception (vibration of left neck muscles) nor caloric-vestibular stimulation (injection of iced water into the left ear) affect covert visual attention in healthy individuals. These results from normals may distinguish between different accounts for unilateral neglect in patients. In particular, they argue against explanations of neglect solely in terms of a pathological misperception of body orientation within an otherwise normal neural representation of space.

Distinguishing sensory and motor biases in parietal and frontal neglect.

Left neglect after right-hemisphere damage may involve perceptual and/or motor impairments. Here we discuss the limitations of previous attempts to separate these components, and introduce a new method. Six neglect patients (three with right inferior parietal lesions and three with right inferior frontal lesions) moved their right hand to a target light, which appeared unpredictably on either the left or the right of central fixation. The target appeared alone or with a distractor light in the opposite hemifield. Any directional motoric bias was measured by comparing reaches from a central start position with those for the same visual displays, but starting from the left of both possible targets (thus requiring only rightward reaches) or from the right (requiring only leftward reaches). All patients were slower to initiate reaches to left than right targets from a central start, which could reflect perceptual and/or motor biases. Critically, in the parietal neglect group only, initiation speed for left targets improved when a rightward reach was required to these (from a left start) rather than a leftward reach. This suggests a deficit in programming leftward movements into left hemispace, in addition to any visual impairment, for parietal neglect. A control task confirmed that this effect of start position was due to the associated change in reach direction and not to afferent inputs from the hand as it rested at the start position. Frontal neglect patients were slow to execute reaches to left targets, regardless of movement direction. Right visual distractors slowed visual reaction times to left targets more than vice versa in frontal neglect patients, and likewise for reach execution times in parietal neglect patients, suggesting that visual distractors on the neglected side have less impact. Distractor effects were unaffected by start position in the frontal neglect group (suggesting a perceptual basis), but distractors slowed reach initiation in the parietal neglect group only from left and central starts. Taken together, these findings demonstrate a directional motor component to parietal but not frontal neglect, and suggest that in man the inferior parietal lobe plays a role not only in perception but also in the programming of selective reaches. These conclusions are related to recent single-unit data from the monkey parietal lobe.

Neural consequences of competing stimuli in both visual hemifields: a physiological basis for visual extinction.

We used positron emission tomography in healthy volunteers to test hemispheric rivalry theories for normal and pathological spatial attention, which provide an influential account of contralesional extinction on bilateral stimulation after unilateral brain injury. Subjects reported visual characters presented either unilaterally or bilaterally. An extinction-like pattern was found behaviorally, with characters in one hemifield reported less accurately when competing characters appeared in the other hemifield. Differences in neural activity for unilateral minus bilateral conditions revealed greater activation of striate and extrastriate areas for stimuli presented without competing stimuli in the other hemifield. Thus, simultaneous bilateral stimulation led to a significant reduction in response by spatiotopic visual cortex contralateral to a particular stimulus. These data provide physiological support for interhemispheric rivalry in the intact human brain, and demonstrate that such competition impacts at early levels of perceptual processing.

Does auditory attention shift in the direction of an upcoming saccade?

In a series of experiments, we examined whether auditory attention shifts in the direction of an upcoming saccade, as recently reported for visual attention. Normal listeners made speeded discriminations for the elevation (up versus down) of abrupt sounds, regardless of their laterality. Each sound was presented around the time that a lateral saccade was made. Auditory elevation discriminations were reliably faster when the saccade was made towards the side of the auditory probe rather than away. Furthermore, an auditory probe on one side speeded up centrally-cued saccades made in that direction, although sounds did not influence saccades to peripheral visual events. The latter visual events were insufficient to affect hearing unless a saccade was made towards them. A further study showed that fixating towards or away from sounds, rather than saccading, could also affect elevation judgements, with poorer performance when fixating away. However, the influence of an upcoming saccade upon hearing could not be reduced to this fixation effect, since the saccade influence was found even for sounds which terminated before any shift in fixation began. Taken together, our results imply that the direction of an upcoming saccade can affect hearing, as can eye-position.

When a rubber hand 'feels' what the real hand cannot.

We examined a patient who was clinically much better at reporting tactile stimulation when he could see his stimulated hand. Experimentally, we found that he had difficulty detecting taps accompanied by a salient (but not predictive) light located directly above his concealed hand. However, his performance was dramatically improved if the light was attached to a rubber hand situated in line with the patient's hidden hand. Previous studies have suggested that tactile sensitivity can be improved by nearby visual stimulation. However, our effect shows that crossmodal sensory facilitation does not only depend upon simple spatial proximity alone. Rather, a simultaneous visual event dramatically improves perception of touch specifically when it is attributed to the perceiver's stimulated limb.

Phasic alerting of neglect patients overcomes their spatial deficit in visual awareness.

Patients with extensive damage to the right hemisphere of their brain often exhibit unilateral neglect of the left side of space. The spatial attention of these patients is strongly biased towards the right, so their awareness of visual events on the left is impaired. Extensive right-hemisphere lesions also impair tonic alertness (the ability to maintain arousal). This nonspatial deficit in alertness is often considered to be a different problem from spatial neglect, but the two impairments may be linked. If so, then phasically increasing the patients' alertness should temporarily ameliorate their spatial bias in awareness. Here we provide evidence to support this theory. Right-hemisphere-neglect patients judged whether a visual event on the left preceded or followed a comparable event on the right. They became aware of left events half a second later than right events on average. This spatial imbalance in the time course of visual awareness was corrected when a warning sound alerted the patients phasically. Even a warning sound on the right accelerated the perception of left visual events in this way. Nonspatial phasic alerting can thus overcome disabling spatial biases in perceptual awareness after brain injury.

Motor role of human inferior parietal lobe revealed in unilateral neglect patients.

The exact role of the parietal lobe in spatial cognition is controversial. One influential hypothesis proposes that it subserves spatial perception, whereas other accounts suggest that its primary role is to direct spatial movement. For humans, it has been suggested that these functions may be divided between inferior and superior parietal lobes, respectively. In apparent support of a purely perceptual function for the inferior parietal lobe (IPL), patients with lesions to this structure, particularly in the right hemisphere, exhibit unilateral spatial neglect (deficient awareness for the side of space opposite to that of their lesion). Here we show that patients with right IPL lesions also have a specific difficulty in initiating leftward movements towards visual targets on the left side of space. This motor impairment was not found in neglect patients with frontal lesions, contrary to previous proposals that motor aspects of neglect are particularly associated with anterior damage. Our results suggest that the human IPL operates as a sensorimotor interface, rather than subserving only perceptual functions.

Visual extinction and prior entry: impaired perception of temporal order with intact motion perception after unilateral parietal damage.

Two patients with left-sided visual extinction after right parietal damage were each given two 'prior entry' tasks that have recently been used to study attentional biases in normals. The first task presented two unconnected bars, one in each visual field, with the patients asked to judge which appeared sooner. Both patients reported that the right bar preceded the left unless the latter led by over 200 msec, suggesting a severe bias to the right affecting the time-course of visual awareness. The second task presented one continuous line in a scrolling format across the same spatial extent, with the patients asked to judge which direction the line moved in. The patients now performed normally. Thus, the perception of temporal order for separate events was impaired by the lesions, but without disrupting motion perception within single events. The implications are discussed for theories of normal and pathological attention, visual awareness, and motion perception.