Functional magnetic resonance imaging of synesthesia: activation of V4/V8 by spoken words.

In 'colored-hearing' synesthesia, individuals report color experiences when they hear spoken words. If the synesthetic color experience resembles that of normal color perception, one would predict activation of parts of the visual system specialized for such perception, namely the human 'color center', referred to as either V4 or V8. Using functional magnetic resonance imaging (fMRI), we here locate the region activated by speech in synesthetes to area V4/V8 in the left hemisphere, and demonstrate overlap with V4/V8 activation in normal controls in response to color. No activity was detected in areas V1 or V2, suggesting that activity in primary visual cortex is not necessary for such experience. Control subjects showed no activity in V4/V8 when imagining colors in response to spoken words, despite overtraining on word-color associations similar to those spontaneously reported by synesthetes.

Diffusion-weighted magnetic resonance imaging detects early neuropathology following four vessel occlusion ischemia in the rat.

Early neuropathology following a prolonged duration of four-vessel occlusion (4 VO) ischemia in the rat was charted using magnetic resonance imaging (MRI). Animals received either 30 minutes of 4 VO (N = 6) or sham operation (N = 6) prior to in vivo assessment. Proton density and T(2) and combined T(2)/diffusion-weighted (T(2)/DW) MRI were performed at 6, 24, and 72 hours postocclusion. T(2)/DW imaging was the most effective sequence for delineating between injured and intact tissues, indicating neuropathology in the dorsolateral striatum at 24 hours and in the CA1/CA2 subfields of the hippocampus at 72 hours following ischemia. Apparent diffusion coefficient values were significantly reduced in the striatum (P = 0.03) and hippocampus (P = 0.005) at 24 and 72 hours, respectively. This is the first report, to our knowledge, of T(2)/DW imaging detecting lesions following 4 VO in accord with the known temporal evolution of ischemic brain damage.

Developmental prosopagnosia: should it be taken at face value?

This study presents a rare case of developmental prosopagnosia. Structural magnetic resonance imaging (MRI) revealed no overt brain abnormalities. EP's basic visual skills and visual memory were intact, as was his ability to judge age, sex and expression from faces, identify facial parts, and make face/non-face decisions. EP was impaired at recognizing famous and very familiar faces and describing visual images of famous faces. He also displayed an anterograde memory impairment for recently studied faces, and performed poorly on tests of unfamiliar face matching, most notably for chimeric faces. It is suggested that EP may be deficient at encoding configural representations of faces. EP appears to have a "pure" (i.e. specific to faces) prosopagnosia, as he shows normal object recognition from unusual viewpoints, good gestalt completion for objects, but not for faces, normal visual imagery for objects but not for faces, a disruption of the inversion effect for faces but not for houses, and performs within the normal range on tests of within-category discriminations, even with unique exemplars of object categories such as famous buildings.

The incidence of schizotypy among cannabis and alcohol users.

Schizotypy research has revealed associations between positive schizotypal symptomatology and substance use but has not related substance use to important schizotypal traits such as anhedonia. Users and nonusers of cannabis and alcohol completed the Oxford-Liverpool Inventory of Feelings and Experiences, the Peters Delusion Inventory, and the Hospital Anxiety and Depression Scale. Cannabis users scored significantly higher on Unusual Experiences, a scale measuring positive schizotypal symptomatology. Both cannabis and alcohol usage were associated with significantly lower scores on Introvertive Anhedonia, which represents negative symptomatology. Delusional ideation and delusional conviction were significantly higher in cannabis users, but for delusional conviction this was only true for users who also drank alcohol. Neither anxiety or depression scores were higher in cannabis users, but delusional ideation correlated with both anxiety and depression, thus providing mixed support for the idea of the "happy schizotype." Overall, these results suggest that cannabis and alcohol usage is related to different dimensions of psychosis-proneness that broadly parallel the relationship between substance use and positive and negative schizophrenic symptoms, thus supporting the continuity view of psychosis and the multidimensionality of psychosis-proneness.

Does frontal lobe activation during retrieval reflect complexity of retrieved information?

Neuroimaging studies of memory have consistently shown that episodic retrieval is associated with right frontal activation, whereas semantic retrieval is associated with left frontal activation. Various hypotheses have been proposed to account for this lateralization in terms of underlying psychological processes. Alternatively, this lateralization may reflect the complexity of information retrieved: retrieval of complex, contextual information accompanying episodic retrieval invokes right-lateralized processes preferentially. We tested this hypothesis by manipulating the type and complexity of information retrieved. Initial increase in complexity of both episodic and semantic information was associated with right inferior frontal activation; further increase in complexity was associated with left dorsolateral activation. We conclude that frontal activation during retrieval is a non-linear function of the complexity of retrieved information.

Differential spatial memory impairment after right temporal lobectomy demonstrated using temporal titration.

In this study a temporal titration method to explore the extent to which spatial memory is differentially impaired following right temporal lobectomy was employed. The spatial and non-spatial memory of 19 left and 19 right temporal lobectomy (TL) patients was compared with that of 16 normal controls. The subjects studied an array of 16 toy objects and were subsequently tested for object recall, object recognition and memory for the location of the objects. By systematically varying the retention intervals for each group, it was possible to match all three groups on object recall at sub-ceiling levels. When memory for the position of the objects was assessed at equivalent delays, the right TL group revealed disrupted spatial memory, compared with both left TL and control groups (P < 0.05). MRI was used to quantify the extent of temporal lobe resection in the two groups and a significant correlation between hippocampal removal and both recall of spatial location and object name recall in the right TL group only was shown. These data support the notion of a selective (but not exclusive) spatial memory impairment associated with right temporal lobe damage that is related to the integrity of the hippocampal functioning.

Storage of verbal associations is sufficient to activate the left medial temporal lobe.

Neuroimaging studies have shown that memory encoding activates the medial temporal lobe (MTL). Many believe that these activations are related to novelty but it remains unproven which is critical - novelty detection or the rich associative encoding it triggers. We examined MTL activation during verbal associative encoding using functional magnetic resonance imaging. First, associative encoding activated left posterior MTL more than single word encoding even though novelty detection was matched, indicating not only that associative encoding activates the MTL particularly strongly, but also that activation does not require novelty detection. Moreover, it remains to be convincingly shown that novelty detection alone does produce such activation. Second, repetitive associative encoding produced less MTL activation than initial associative encoding, indicating that priming of associative information reduces MTL activation. Third, re-encoding familiar associations in a well-established way had a minimal effect on both memory and MTL activation, indicating that MTL activation reflects storage of associations, not merely their initial representation.

Selective spatial memory impairment after right unilateral temporal lobectomy.

Deficits in performance of both spatial and visual tasks are common following tissue loss in the right temporal lobe. Since spatial and visual attributes are frequently confounded in experimental tasks, we have studied patients following unilateral temporal lobectomy, in an attempt to determine which aspect mediates the observed deficits. Spatial and visual memory performance was compared in normal controls (n = 16), left temporal (LTL; n = 19) and right temporal (RTL; n = 19) lobectomy patients, by presentation of eight abstract designs in a spatial array for subsequent recall and recognition of the designs (visual memory) and recall of their spatial position (spatial memory). By varying the retention intervals for each group, all three groups were matched on both recall and recognition of the designs at sub-ceiling levels. In contrast, recall of the position of the designs (spatial memory), tested at equivalent delays to those of the visual memory tests, revealed a deficit in the RTL patients compared to both controls and LTL patients (p < 0.05). Magnetic resonance imaging (MRI) was used to quantify the extent of resection of the hippocampus and parahippocampal regions in the two patient groups and showed a significant correlation between hippocampal and parahippocampal removal and spatial memory in the RTL group only. These data support the notion of a disproportionately large involvement of the right hippocampus and adjacent regions in spatial memory.

Neurotoxic dorsal CA1 lesions versus 4 VO ischaemic lesions: behavioural comparisons.

Anterograde amnesia, a common consequence of transient cerebral ischaemia, has been attributed to cell loss in the hippocampal CA1 subfield. However, variable, widespread damage outside hippocampal CA1 can also occur following ischaemia. We compared the functional consequences of ischaemia and ibotenate acid CA1 lesions on 2 spatial memory tasks (water maze 'place' and 'matching-to-position') to address the possibility that extra-CA1 loss contributes to ischaemia-induced memory deficits in the rat. During place task acquisition, ischaemic rats showed deficits on more measures than ibotenic rats, and during a 1 min probe trial, only ischaemic rats were impaired. On the matching-to-position task, ibotenic rats showed greater impairment than ischaemic rats in terms of one-trial learning, whereas ischaemic rats were more impaired after Trial 2. Ischaemia and ibotenic acid lesions resulted in equivalent CA1 loss, but silver impregnation revealed additional extra-CA1 cell loss in ischaemic rats. Together with the greater behavioural deficits of ischaemic rats, these data indicate a role for extra-CA1 cell loss in ischaemia-induced memory impairments in both animals and humans.

Silver impregnation reveals neuronal damage in cingulate cortex following 4 VO ischaemia in the rat.

An intriguing feature of global ischaemic cell loss is the sensitivity of certain neuronal populations and the relative resistance of others. Silver impregnation was used to ascertain the pattern and extent of cell loss following 15 min 4 VO ischaemia in the rat. Cell loss was observed primarily in the CA1 region of the hippocampus, as assessed by both cresyl violet and silver stains. However, degenerating neurones were most readily identifiable when impregnated with silver, and additional regions of neuronal loss were selectively revealed by silver staining in the hippocampal hilar region, dorsolateral striatum, neocortex and cingulate cortex. Damage to cingulate is a hitherto unreported consequence of 4 VO global ischaemia. This novel finding may have implications for ischaemic brain-behaviour relationships.

Global ischaemia: hippocampal pathology and spatial deficits in the water maze.

Spatial deficits were assessed in male Wistar rats which had undergone 4 vessel occlusion for 5, 10, 15 or 30 min. Relationships between the extent of brain damage, the duration of 4-vessel occlusion, and the behavioural impairment consequent upon ischaemia were investigated. Starting 13-18 days after occlusion, rats were trained to find a hidden platform in a Morris water maze. All ischaemic groups were impaired on some performance indices relative to controls, in both acquisition and retention of the platform location. Increasing the duration of ischaemia increased behavioural deficits on some measures, but there was no clear-cut evidence that longer durations of ischaemia resulted in increased behavioural impairments. Histological assessment, at two coronal levels in hippocampus and four coronal levels in cortex and striatum, revealed CA1 cell loss in all ischaemic groups, which varied between 10-100% across the range of durations employed. CA1 cell loss increased as both a linear and quadratic function of increasing the duration of ischaemia. In rats subjected to 5-15 min ischaemia, cell loss was almost exclusively confined to the CA1 area. In rats subjected to 30 min ischaemia there was additional, variable damage in hippocampal areas CA2, 3 and 4, substantial cell loss in the striatum (50-70%) and some neuronal damage in the cortex (largely in layer III). However correlations between CA1 cell loss in ischaemic rats and indices of spatial ability were non-significant, despite avoiding bias in the analysis by ensuring that only those rats with submaximal CA1 cell loss estimates and behavioural impairments were included. Given the lack of correlation between damage to the CA1 region and behaviour, it is suggested that CA1 cell loss may not be the only determinant of the water maze deficits displayed by 4-vessel occlusion ischaemic rats.