Reduced thalamic volume in men with antisocial personality disorder or schizophrenia and a history of serious violence and childhood abuse.

OBJECTIVE: Violent behaviour has been associated with presence of certain mental disorders, most notably antisocial personality disorder (ASPD) and schizophrenia, childhood abuse, and multiple brain abnormalities. This study examined for the first time, to the authors' knowledge, the role of psychosocial deprivation (PSD), including childhood physical and sexual abuse, in structural brain volumes of violent individuals with ASPD or schizophrenia. METHODS: Fifty-six men (26 with ASPD or schizophrenia and a history of serious violence, 30 non-violent) underwent magnetic resonance imaging and were assessed on PSD. Stereological volumetric brain ratings were examined for group differences and their association with PSD ratings. PSD-brain associations were examined further using voxel-based-morphometry. RESULTS: The findings revealed: reduced thalamic volume in psychosocially-deprived violent individuals, relative to non-deprived violent individuals and healthy controls; negative association between thalamic volume and abuse ratings (physical and sexual) in violent individuals; and trend-level negative associations between PSD and hippocampal and prefrontal volumes in non-violent individuals. The voxel-based-morphometry analysis detected a negative association between PSD and localised grey matter volumes in the left inferior frontal region across all individuals, and additionally in the left middle frontal and precentral gyri in non-violent individuals. CONCLUSIONS: Violent mentally-disordered individuals with PSD, relative to those with no or minimal PSD, suffer from an additional brain deficit, i.e., reduced thalamic volume; this may affect sensory information processing, and have implications for management, of these individuals. PSD may have a stronger relationship with volumetric loss of stress-linked regions, namely the frontal cortex, in non-violent individuals.

Backward and forward visual masking in schizophrenia and its relation to global motion and global form perception.

Whilst visual backward masking deficits in schizophrenia have been reliably reported and may reveal magnocellular dysfunction, forward masking, which may rely more heavily on the parvocellular system, has been under investigated. In a group of 64 schizophrenia patients and 65 matched controls we undertook a visual masking paradigm containing both conditions, together with tests of 'global motion' and 'global form' perception, two 'down-stream' visual tasks reflecting later processing linked to magnocellular and parvocellular function respectively. In the patient group, a significant but small deficit on the masking task, equivalent across forward and backward conditions was seen. Correlations between the masking and motion/form tasks supported the predominant theoretical framework describing the neural processes involved in masking. Performance on the motion and form tasks was differentiated by a trend-level motion processing deficit but near-normal form processing. The results suggest an 'early visual' processing deficit in both magno- and parvocellular systems but one which is only transferred to 'down-stream' processing areas with predominantly magnocellular input.

Persecutory delusions and the determination of self-relevance: an fMRI investigation.

BACKGROUND: People with persecutory delusions regard ambiguous data in the social domain as self-relevant and selectively attend to threatening information. This study aimed to characterize these social cognitive biases in functional neuroanatomical terms. METHOD: Eight schizophrenic patients with active persecutory delusions and eight matched normal controls underwent functional magnetic resonance imaging while determining the self-relevance of ambiguous self-relevant or unambiguous other-relevant neutral and threatening statements. RESULTS: In determining self-relevance, the deluded subjects showed a marked absence of rostral-ventral anterior cingulate activation together with increased posterior cingulate gyrus activation in comparison to the normal subjects. The influence of threat on self-relevance determination did not yield statistically significant differences between deluded and normal subjects. CONCLUSIONS: Abnormalities of cingulate gyrus activation while determining self-relevance suggest impaired self-reflection in the persecutory deluded state. This may contribute to persecutory belief formation and maintenance.

Visual command hallucinations in a patient with pure alexia.

Around 25% of patients with visual hallucinations secondary to eye disease report hallucinations of text. The hallucinated text conveys little if any meaning, typically consisting of individual letters, words, or nonsense letter strings (orthographic hallucinations). A patient is described with textual visual hallucinations of a very different linguistic content following bilateral occipito-temporal infarcts. The hallucinations consisted of grammatically correct, meaningful written sentences or phrases, often in the second person and with a threatening and command-like nature (syntacto-semantic visual hallucinations). A detailed phenomenological interview and visual psychophysical testing were undertaken. The patient showed a classical ventral occipito-temporal syndrome with achromatopsia, prosopagnosia, and associative visual agnosia. Of particular significance was the presence of pure alexia. Illusions of colour induced by monochromatic gratings and a novel motion-direction illusion were also observed, both consistent with the residual capacities of the patient's spared visual cortex. The content of orthographic visual hallucinations matches the known specialisations of an area in the left posterior fusiform gyrus--the visual word form area (VWFA)--suggesting the two are related. The VWFA is unlikely to be responsible for the syntacto-semantic hallucinations described here as the patient had a pure alexic syndrome, a known consequence of VWFA lesions. Syntacto-semantic visual hallucinations may represent a separate category of textual hallucinations related to the cortical network implicated in the auditory hallucinations of schizophrenia.

fMRI BOLD response to increasing task difficulty during successful paired associates learning.

We used functional magnetic resonance imaging (fMRI) to assess cortical activations associated with increasing task difficulty (TD) in a visuospatial paired associates learning task. Encoding and retrieval were examined when 100% successful retrieval of three, four, or six object-location pairs had been attained (thus ensuring that performance was matched across subjects). As memory load increased, in general, the number of attempts taken to achieve 100% successful retrieval increased, while the number of trials correctly completed on the first attempt decreased. By modelling parametric variations in working memory load with BOLD signal changes we were able to identify brain regions displaying linear and nonlinear responses to increasing load. During encoding, load-independent activations were found in occipitoparietal cortices (excluding the precuneus for which linear load dependency was demonstrated), anterior cingulate, and cerebellum, while linear load-dependent activations in these same regions were found during retrieval. Nonlinear load-dependent responses, as identified by categorical contrasts between levels of load, were found in the right DLPFC and left inferior frontal gyrus. The cortical response to increasing cognitive demands or TD appears to involve the same, rather than an additional, network of brain regions "working harder."

Self-responsibility and the self-serving bias: an fMRI investigation of causal attributions.

We use causal attributions to infer the most likely cause of events in the social world. Internal attributions imply self-responsibility for events. The self-serving bias describes the tendency of normal subjects to attribute the causation of positive events internally ("I am responsible em leader ") and negative events externally ("Other people or situational factors are responsible em leader "). The self-serving bias has been assumed to serve a positive motivational function by enhancing self-esteem. Abnormalities of attributional style have been implicated in both depression and psychosis. We examined the neural basis of both self-responsibility and the self-serving bias using functional magnetic resonance imaging during the performance of attributional decision tasks. We found that the determination of self-responsibility recruits areas previously implicated in action simulation (bilateral premotor cortex and cerebellum), suggesting that such higher order social cognition is related to simpler internal models of goal-directed action. The dorsal striatum, previously implicated in motivated behavior, mediates the self-serving bias.

Functional imaging of the mechanisms underlying the bilateral field advantage.

Visual stimulus comparisons across the vertical meridian are faster and more accurate than those restricted to a single hemifield (the bilateral field advantage). We set out to investigate the cerebral mechanisms underlying this effect using functional magnetic resonance imaging. Seven normal volunteers were presented pairs of shape stimuli bilaterally across the vertical meridian and unilaterally within a single hemifield. We found a network of additional areas activated in the unilateral condition over the bilateral condition which have been related to working memory in previous studies. The results suggest different processing strategies with different temporal characteristics in the bilateral and unilateral conditions, providing a novel explanation for the bilateral field advantage.

The functional significance of perinatal corpus callosum damage: an fMRI study in young adults.

We used functional MRI (fMRI) to establish the functional significance of corpus callosum damage in young adults who had been born very preterm. Seven subjects from a cohort of individuals who had been born at <33 weeks gestation and who had sustained callosal damage visualized on structural MRI were compared while they carried out auditory and visual tasks requiring callosal transfer with nine very preterm subjects with corpora callosa of normal appearance on structural MRI, and with seven full-term controls. The very preterm subjects with damaged corpora callosa had significantly different activation patterns compared with the two control groups. In the visual task, additional activity was seen in the right dorsolateral prefrontal cortex of the damaged callosum group, possibly because the task was accomplished by storing information in working memory. On the auditory task, a deficit of activity was seen in the right temporal lobe of the callosum group. The findings reveal a plasticity of function compensating for early damage to the corpus callosum.

Imaging attentional and attributional bias: an fMRI approach to the paranoid delusion.

BACKGROUND: The pathophysiology of auditory hallucinations and delusions of control has been elucidated using functional imaging. Despite their clinical importance, there have been few similar attempts to investigate paranoid delusions. We have examined two components of social cognition (attentional and attributional biases) that contribute to the formation and maintenance of paranoid delusions, using functional magnetic resonance imaging (fMRI). METHOD: Normal subjects performed tasks requiring attentional and attributional judgements. We investigated the neural response particularly associated with attention to threatening material relevant to self and with the 'self-serving' attributional bias. RESULTS: The determination of relevance to self of verbal statements of differing emotional valence involved left ventrolateral prefrontal cortex (left inferior frontal gyrus, BA 47), right caudate and right cingulate gyrus (BA 24). Attention to threatening material relevant to self differentially activated a more dorsal region of the left inferior frontal gyrus (BA 44). Internal attributions of events, where the self was viewed as an active intentional agent, involved left precentral gyrus (BA 6) and left middle temporal gyrus (BA 39). Attribution of events in a non 'self-serving' manner required activation of the left precentral gyrus (BA 6). CONCLUSIONS: Anomalous activity or connectivity within these defined regions may account for the attentional or attributional biases subserving paranoid delusion formation. This provides a simple model for paranoid delusion formation that can be tested in patients.

Visual hallucinatory syndromes and the anatomy of the visual brain.

We have set out to identify phenomenological correlates of cerebral functional architecture within Charles Bonnet syndrome (CBS) hallucinations by looking for associations between specific hallucination categories. Thirty-four CBS patients were examined with a structured interview/questionnaire to establish the presence of 28 different pathological visual experiences. Associations between categories of pathological experience were investigated by an exploratory factor analysis. Twelve of the pathological experiences partitioned into three segregated syndromic clusters. The first cluster consisted of hallucinations of extended landscape scenes and small figures in costumes with hats; the second, hallucinations of grotesque, disembodied and distorted faces with prominent eyes and teeth; and the third, visual perseveration and delayed palinopsia. The three visual psycho-syndromes mirror the segregation of hierarchical visual pathways into streams and suggest a novel theoretical framework for future research into the pathophysiology of neuropsychiatric syndromes.

Human area V5 and motion in the ipsilateral visual field.

We have studied area V5 of the human brain with visually-evoked potential (VEP) and functional magnetic resonance imaging (fMRI) methods, using hemifield motion stimuli. Our results confirmed the presence of an ipsilateral field representation in V5 and found: (i) a delay in the ipsilateral response in V5, irrespective of the hemifield stimulated; (ii) a longer ipsilateral delay for left hemifield than for right hemifield stimulation; and (iii) in a patient with a section of the splenium, an absent ipsilateral response for right but not left hemifield stimulation. Together with neurophysiological and anatomical evidence in the monkey, our non-invasive spatial and temporal imaging studies in man reveal that ipsilateral V5 is activated by motion signals transferred from contralateral V5. The asymmetry of ipsilateral delay in normal subjects and the asymmetrical loss of ipsilateral response following splenial section imply that signals related to visual motion are transferred from one V5 to the other through two segregated pathways.

fMRI and EEG responses to periodic visual stimulation.

EEG/VEP and fMRI responses to periodic visual stimulation are reported. The purpose of these experiments was to look for similar patterns in the time series produced by each method to help understand the relationship between the two. The stimulation protocol was the same for both sets of experiments and consisted of five complete cycles of checkerboard pattern reversal at 1.87 Hz for 30 s followed by 30 s of a stationary checkerboard. The fMRI data was analyzed using standard methods, while the EEG was analyzed with a new measurement of activation-the VEPEG. Both VEPEG and fMRI time series contain the fundamental frequency of the stimulus and quasi harmonic components-an unexplained double frequency commonly found in fMRI data. These results have prompted a reappraisal of the methods for analyzing fMRI data and have suggested a connection between our findings and much older published invasive electrophysiological measurements of blood flow and the partial pressures of oxygen and carbon dioxide. Overall our new analysis suggests that fMRI signals are strongly dependant on hydraulic blood flow effects. We distinguish three categories of fMRI signal corresponding to: focal activated regions of brain tissue; diffuse nonspecific regions of steal; and major cerebral vessels of arterial supply or venous drainage. Each category of signal has its own finger print in frequency, amplitude, and phase. Finally, we put forward the hypothesis that modulations in blood flow are not only the consequence but are also the cause of modulations in functional activity.

The perceptual consequences of visual loss: 'positive' pathologies of vision.

Fifty patients with visual hallucinations and illusions secondary to degenerative eye disease reported remarkably stereotyped experiences. Questionnaire responses revealed five previously recognized categories of pathological vision (perseveration, illusory visual spread, polyopia, prosopometamorphopsia and micro/macropsia) and three novel categories (tessellopsia, hyperchromatopsia and dendropsia). Identical pathologies of vision occur in a range of clinical and experimental settings, suggesting that they reflect fundamental visual processes. The known neurophysiology of the visual cortex helps explain the phenomenology of the experiences and provides the basis for a neurobiologically based classification of positive and negative visual perceptual disorders.

The functional anatomy of imagining and perceiving colour.

We report two functional magnetic resonance imaging experiments which reveal similarities and differences between perceptual and imaginal networks within the single visual submodality of colour. The first experiment contrasted viewing of a coloured and grey-scale Mondrian display, while the second contrasted a relative colour judgement with a spatial task and required the generation of mental images. Our results show that colour perception activates the posterior fusiform gyrus bilaterally (area V4), plus right-sided anterior fusiform and lingual gyri, striate cortex (area V1), and the left and right insula. Colour imagery activated right anterior fusiform gyrus, left insula, right hippocampus and parahippocampal gyrus, but not V4 or V1. The findings reconcile neurological case studies suggesting a double dissociation between deficits in colour imagery and perception and point to anterior fusiform, parahippocampal gyri and hippocampus as the location for stored representations of coloured objects.

The Riddoch syndrome: insights into the neurobiology of conscious vision.

We have studied a patient, G.Y., who was rendered hemianopic following a lesion affecting the primary visual cortex (area VI), sustained 31 years ago, with the hope of characterizing his ability to discriminate visual stimuli presented in his blind field, both psychophysically and in terms of the brain activity revealed by imaging methods. Our results show that (i) there is a correlation between G.Y.'s capacity to discriminate stimuli presented in his blind field and his conscious awareness of the same stimuli and (ii) that G.Y.'s performance on some tasks is characterized by a marked variability, both in terms of his awareness for a given level of discrimination and in his discrimination for a given level of awareness. The observations on G.Y., and a comparison of his capacities with those of normal subjects, leads us to propose a simple model of the relationship between visual discrimination and awareness. This supposes that the two independent capacities are very tightly coupled in normal subjects (gnosopsia) and that the effect of a VI lesion is to uncouple them, but only slightly. This uncoupling leads to two symmetrical departures, on the one hand to gnosanopsia (awareness without discrimination) and on the other to agnosopsia (discrimination without awareness). Our functional MRI studies show that V5 is always active when moving stimuli, whether slow or fast, are presented to his blind field and that the activity in V5 co-varies with less intense activity in other cortical areas. The difference in cerebral activity between gnosopsia and agnosopsia is that, in the latter, the activity in V5 is less intense and lower statistical thresholds are required to demonstrate it. Direct comparison of the brain activity during individual 'aware' and 'unaware' trials, corrected for the confounding effects of motion, has also allowed us, for the first time, to titrate conscious awareness against brain activity and show that there is a straightforward relationship between awareness and activity, both in individual cortical areas, in this case area V5, and in the reticular activating system. The imaging evidence, together with the variability in his levels of awareness and discrimination, manifested in his capacity to discriminate consciously on some occasions and unconsciously on others, leads us to conclude that agnosopsia, gnosopsia and gnosanopsia are all manifestations of a single condition which we call the Riddoch syndrome, in deference to the British neurologist who, in 1917, first characterized the major aspect of this disability. We discuss the significance of these results in relation to historical views about the organization of the visual brain.

The anatomy of conscious vision: an fMRI study of visual hallucinations.

Despite recent advances in functional neuroimaging, the apparently simple question of how and where we see--the neurobiology of visual consciousness--continues to challenge neuroscientists. Without a method to differentiate neural processing specific to consciousness from unconscious afferent sensory signals, the issue has been difficult to resolve experimentally. Here we use functional magnetic resonance imaging (fMRI) to study patients with the Charles Bonnet syndrome, for whom visual perception and sensory input have become dissociated. We found that hallucinations of color, faces, textures and objects correlate with cerebral activity in ventral extrastriate visual cortex, that the content of the hallucinations reflects the functional specializations of the region and that patients who hallucinate have increased ventral extrastriate activity, which persists between hallucinations.

Motion specific responses from a blind hemifield.

In a previous study we showed that fast moving stimuli activate V5, an area specialized for motion, at very short latencies through a pathway that reaches it without passing through V1. Using the same technique of visual evoked responses, we have tested our conclusions by studying patient GY, whose V1 is damaged but whose V5 is intact. In spite of the contralateral hemi-blindness due to his V1 lesion, GY has a residual visual capacity that allows him to perceive, consciously, fast but not slow moving stimuli presented in his affected hemifield. By stimulating GY's 'blind' hemifield and comparing the responses with those obtained from normal subjects, we were able to study the relative contribution of V1 and V5 to the visual evoked response to motion in normal subjects. We found that GY's early response to fast motion is preserved and correlates with activity elicited in control subjects over area V5, while slow motion, pattern offset, and pattern reversal stimuli failed to elicit responses in GY. The results confirm our previous conclusions: namely, that the early part of the motion evoked response is generated in area V5 and that signals reach this area through a dynamically parallel pathway that bypasses area V1. They go on to demonstrate that neurophysiological activity in the prestriate cortex correlates with the conscious visual perception of motion.