Iona Alexander

Attentional selection and action selection in the ventral and orbital prefrontal cortex.

Different accounts of the ventral and orbital prefrontal cortex (PFv+o) have emphasized either its role in learning conditional rules for action selection or the attentional selection of behaviorally relevant stimuli. Although the accounts are not mutually exclusive, it is possible that the involvement of PFv+o in conditional action selection is a consequence of its role in selecting relevant stimuli or that its involvement in attentional selection is a consequence of the conditional rules present in many attentional paradigms. Five macaques learned a conditional action-selection task in which the difficulty of identifying the stimulus relevant for guiding action selection was varied in a simple manner by either altering its distance from the action or presenting additional distracting stimuli. Simply increasing the spatial separation between the instructing stimulus led to slower responses. Experiment 1 showed that bilateral PFv+o lesions impaired conditional action selection even when attentional demands were kept to a minimum, but there was evidence that the impairment was exacerbated by manipulating stimulus selection difficulty. Experiment 2 confirmed the importance of PFv+o for conditional action selection even when stimulus selection difficulty was minimal. Experiments 3 and 4 demonstrated that the action-selection impairment was significantly increased by making identification of the behaviorally relevant stimulus difficult. PFv+o is central to the use of conditional rules when selecting courses of action, but conditional rules are also represented in premotor and striatal regions. A special contribution of PFv+o may be initial selection of behaviorally relevant stimuli.

Transneuronal retrograde degeneration of retinal ganglion cells and optic tract in hemianopic monkeys and humans

Transneuronal retrograde degeneration of retinal ganglion cells after removal of primary visual cortex (area V1) is well established by quantitative neurohistological analysis of the ganglion cell layer in monkeys, but remains controversial in human patients. Therefore, we first histologically examined retinal degeneration in sectioned archived retinae of 26 macaque monkeys with unilateral V1 ablation and post-surgical survival times ranging from 3 months to 14.3 years. In addition, the cross-sectional area of the optic tract was measured in archived coronal histological sections of the brain of every hemianopic monkey and in sections from 10 control monkeys with non-visual bilateral cortical lesions. The ratios of nasal and temporal retinal ganglion cell counts in the contralesional eye and ipsi/contralateral optic tract areas were calculated and compared. They show that the decline was initially more pronounced for the optic tract, slackened after 3 years post-lesion and was steeper for the ganglion cells thereafter. Nevertheless, both measures were highly correlated. Second, we calculated ratios from structural magnetic resonance images to see whether the optic tracts of four human hemianopes would show similar evidence of transneuronal degeneration of their ipsilesional optic tract. The results were consistent with extensive and time-dependent degeneration of the retinal ganglion cell layer. The measures of the optic tracts provide evidence for comparable transneuronal retinal ganglion cell degeneration in both primate species and show that structural magnetic resonance image can both reveal and assess it.

The right parietal cortex and time perception: back to Critchley and the Zeitraffer phenomenon.

We investigated the involvement of the posterior parietal cortex in time perception by temporarily disrupting normal functioning in this region, in subjects making prospective judgements of time or pitch. Disruption of the right posterior parietal cortex significantly slowed reaction times when making time, but not pitch, judgements. Similar interference with the left parietal cortex and control stimulation over the vertex did not significantly change performance on either pitch or time tasks. The results show that the information processing necessary for temporal judgements involves the parietal cortex, probably to optimise spatiotemporal accuracy in voluntary action. The results are in agreement with a recent neuroimaging study and are discussed with regard to a psychological model of temporal processing and a recent proposal that time is part of a parietal cortex system for encoding magnitude information relevant for action.

Cortico-basal ganglia pathways are essential for the recall of well-established visuomotor associations.

Recent human neuroimaging studies, supported by lesion studies with nonhuman primates, have suggested that learning arbitrary associations between sensory cues and behavioural responses requires interactions between the infero‐temporal, prefrontal and premotor cortices. We directly tested the hypothesis suggested from our neuroimaging experiments that functional links between the basal ganglia and premotor cortex are involved in the process via which task performance becomes automatic. We made unilateral excitotoxic lesions, centred on the internal pallidum, in four macaques previously given extensive experience on the associations between nonspatial visual cues and movements of a joystick. The basal ganglia lesion was later combined with a premotor cortical lesion in the opposite hemisphere so as to interrupt the connections between them. Three of the animals were subsequently found to be impaired in relearning pre‐operatively acquired associations; they eventually succeeded but made three‐times as many errors. A fourth animal was unimpaired but its premotor cortex lesion was later found to be incomplete. Response times were only marginally increased and the learning of novel associations appeared relatively unaffected by these lesions. As a control, the effects of a unilateral premotor cortex lesion were assessed with two additional animals but this lesion did not result in a relearning impairment. We therefore suggest that when visuomotor associations have become well established through over‐training, performance depends on connections between the basal ganglia and premotor cortex.

Reduced chromatic discrimination in children with autism spectrum disorders

Atypical perception in Autism Spectrum Disorders (ASD) is well documented (Dakin & Frith, 2005). However, relatively little is known about colour perception in ASD. Less accurate performance on certain colour tasks has led some to argue that chromatic discrimination is reduced in ASD relative to typical development (Franklin, Sowden, Burley, Notman & Alder, 2008). The current investigation assessed chromatic discrimination in children with high-functioning autism (HFA) and typically developing (TD) children matched on age and non-verbal cognitive ability, using the Farnsworth-Munsell 100 hue test (Experiment 1) and a threshold discrimination task (Experiment 2). In Experiment 1, more errors on the chromatic discrimination task were made by the HFA than the TD group. Comparison with test norms revealed that performance for the HFA group was at a similar level to typically developing children around 3 years younger. In Experiment 2, chromatic thresholds were elevated for the HFA group relative to the TD group. For both experiments, reduced chromatic discrimination in ASD was due to a general reduction in chromatic sensitivity rather than a specific difficulty with either red-green or blue-yellow subsystems of colour vision. The absence of group differences on control tasks ruled out an explanation in terms of general task ability rather than chromatic sensitivity. Theories to account for the reduction in chromatic discrimination in HFA are discussed, and findings are related to cortical models of perceptual processing in ASD.

Impact of Cataract Surgery on Sleep in Patients Receiving Either Ultraviolet-Blocking or Blue-Filtering Intraocular Lens Implants

PURPOSE Although visual impairment is a well-recognized consequence of cataract development, little is known about the ability of the melanopsin-based photosensitive retinal ganglion cells (pRGCs) to regulate sleep-wake timing in the presence of cataract. In this study, we replaced a cataractous natural crystalline lens with two different types of artificial intraocular lenses, a UV-blocking lens or a blue-filtering lens. We investigated the level of sleep disturbance before cataract surgery and any change in sleep due to improved light transmission following surgery and compared this in both types of intraocular lens. METHODS Quality of sleep in 961 patients undergoing cataract surgery was assessed by administering the validated self-reported Pittsburgh Sleep Quality Index (PSQI) questionnaire. The PSQI distinguishes good sleepers from poor sleepers by scoring seven different sleep components over the last month, which are combined to produce an overall score for sleep quality. Patients received either an ultraviolet-blocking (UVB) clear intraocular lens (IOL) or a blue-filtering (BF) IOL. Questionnaires were completed four times: 1 month preoperatively and again 1, 6 (UVB-IOL only), and 12 months postoperatively. RESULTS Half of the patients reported poor sleep in the presence of cataract in both the UVB-IOL (mean PSQI = 6.35; SD = 3.82) and BF-IOL (mean PSQI = 6.39; SD = 4.04) groups. Cataract removal improved overall sleep quality significantly 1 month postoperatively in the UVB-IOL (mean PSQI = 5.89; SD = 3.71) and BF-IOL (mean PSQI = 6.08; SD = 3.88) groups. Sleep latency also improved for the UVB-IOL (preoperative mean = 1.16; SD = 1.003) and BF-IOL (preoperative mean = 1.17; SD = 1.03) groups at 1 month (UVB-IOL group mean = 1.01; SD = 0.923 and BF-IOL group mean = 1.00; SD = 0.95), which was sustained at 6 months for the UVB-IOL group (mean = 1.02; SD = 0.93) and 12 months for both the UVB-IOL and BF-IOL groups (6 months: UVB-IOL group mean = 0.96; SD = 0.92 and for the BF-IOL group mean = 0.99; SD = 0.96). CONCLUSIONS Overall sleep quality and sleep latency improves after removal of cataract irrespective of the type of IOL implanted. These data show that implantation of BF-IOL does not have a negative impact on the sleep-wake cycle.

Visual activation of extra-striate cortex in the absence of V1 activation.

Research highlights ▶ Gray matter of V1 shows abnormal T1 characteristics and its perfusion is reduced. ▶ Damage is confined to gray matter with no adjacent white matter involvement. ▶ BOLD activation levels in the calcarine sulcus are drastically reduced. ▶ Activation of extrastriate regions to visual stimulation is preserved. ▶ Pathway between LGN and V1 shows degeneration; between LGN and V5/MT is intact.

Early Auditory Processing in Area V5/MT+ of the Congenitally Blind Brain

Previous imaging studies of congenital blindness have studied individuals with heterogeneous causes of blindness, which may influence the nature and extent of cross-modal plasticity. Here, we scanned a homogeneous group of blind people with bilateral congenital anophthalmia, a condition in which both eyes fail to develop, and, as a result, the visual pathway is not stimulated by either light or retinal waves. This model of congenital blindness presents an opportunity to investigate the effects of very early visual deafferentation on the functional organization of the brain. In anophthalmic animals, the occipital cortex receives direct subcortical auditory input. We hypothesized that this pattern of subcortical reorganization ought to result in a topographic mapping of auditory frequency information in the occipital cortex of anophthalmic people. Using functional MRI, we examined auditory-evoked activity to pure tones of high, medium, and low frequencies. Activity in the superior temporal cortex was significantly reduced in anophthalmic compared with sighted participants. In the occipital cortex, a region corresponding to the cytoarchitectural area V5/MT+ was activated in the anophthalmic participants but not in sighted controls. Whereas previous studies in the blind indicate that this cortical area is activated to auditory motion, our data show it is also active for trains of pure tone stimuli and in some anophthalmic participants shows a topographic mapping (tonotopy). Therefore, this region appears to be performing early sensory processing, possibly served by direct subcortical input from the pulvinar to V5/MT+.

Edges, colour and awareness in blindsight.

It remains unclear what is being processed in blindsight in response to faces, colours, shapes, and patterns. This was investigated in two hemianopes with chromatic and achromatic stimuli with sharp or shallow luminance or chromatic contrast boundaries or temporal onsets. Performance was excellent only when stimuli had sharp spatial boundaries. When discrimination between isoluminant coloured Gaussians was good it declined to chance levels if stimulus onset was slow. The ability to discriminate between instantaneously presented colours in the hemianopic field depended on their luminance, indicating that wavelength discrimination totally independent of other stimulus qualities is absent. When presented with narrow-band colours the hemianopes detected a stimulus maximally effective for S-cones but invisible to M- and L-cones, indicating that blindsight is mediated not just by the mid-brain, which receives no S-cone input, or that the rods contribute to blindsight. The results show that only simple stimulus features are processed in blindsight.

The cortical basis of global motion detection in blindsight

The importance of stimulus qualities such as orientation, motion and luminance in blindsight are well known but their cortical basis has been much less explored. We therefore studied the performance of two blindsighted hemianopic subjects (GY and MS), in a task in which the subject had to decide in which of two adjunctive intervals a pattern of global spots moved coherently, at a variety of speeds, in the hemianopic field. Their ability was compared with that of two control subjects with normal vision. Both hemianopes performed this simple discrimination well in their blind fields but their performance was impaired by repetitive transcranial magnetic stimulation (rTMS) applied over cortical area hV5/MT+ although not, or only slightly, by stimulation over the region of V3 or the vertex. The result is a direct demonstration that area hV5/MT+ is necessary for global motion detection in blindsight.