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Background: Anorexia nervosa (AN) is a serious psychiatric illness that remains difficult to treat. Elucidating the neural mechanisms of AN is necessary to identify novel treatment targets and improve outcomes. A growing body of literature points to a role for dorsal fronto-striatal circuitry in the pathophysiology of AN, with increasing evidence of abnormal task-based fMRI activation within this network among patients with AN. Whether these abnormalities are present at rest and reflect fundamental differences in brain organization is unclear., Methods: The current study combined resting-state fMRI data from patients with AN ( n = 89) and healthy controls (HC; n = 92) across four studies, removing site effects using ComBat harmonization. First, the a priori hypothesis that dorsal fronto-striatal connectivity strength - specifically between the anterior caudate and dlPFC - differed between patients and HC was tested using seed-based functional connectivity analysis with small-volume correction. To assess specificity of effects, exploratory analyses examined anterior caudate whole-brain connectivity, amplitude of low-frequency fluctuations (ALFF), and node centrality., Results: Compared to HC, patients showed significantly reduced right, but not left, anterior caudate-dlPFC connectivity ( p = 0.002) in small-volume corrected analyses. Whole-brain analyses also identified reduced connectivity between the right anterior caudate and left superior frontal and middle frontal gyri ( p = 0.028) and increased connectivity between the right anterior caudate and right occipital cortex ( p = 0.038). No group differences were found in analyses of anterior caudate ALFF and node centrality., Conclusions: Decreased coupling of dorsal fronto-striatal regions indicates that circuit-based abnormalities persist at rest and suggests this network may be a potential treatment target.

Background: Abnormalities in reward learning in psychotic disorders have been proposed to be linked to dysregulated subcortical dopaminergic (DA) neurotransmission, which in turn is a suspected mechanism for predisposition to psychosis. We therefore explored the striatal dopaminergic modulation of reward processing and its behavioral correlates in individuals at familial risk for psychosis., Methods: We performed a DA D2/3 receptor [18F]fallypride positron emission tomography scan during a probabilistic reinforcement learning task in 16 healthy first-degree relatives of patients with psychosis and 16 healthy volunteers, followed by a 6-day ecological momentary assessment study capturing reward-oriented behavior in the everyday life., Results: We detected significant reward-induced DA release in bilateral caudate, putamen and ventral striatum of both groups, with no group differences in its magnitude nor spatial extent. In both groups alike, greater extent of reward-induced DA release in all regions of interest was associated with better performance in the task, as well as in greater tendency to be engaged in reward-oriented behavior in the daily life., Conclusions: These findings suggest intact striatal dopaminergic modulation of reinforcement learning and reward-oriented behavior in individuals with familial predisposition to psychosis. Furthermore, this study points towards a key link between striatal reward-related DA release and pursuit of ecologically relevant rewards.

Background: Commonly observed distortions in decision-making among patients with major depressive disorder (MDD) may emerge from impaired reward processing and cognitive biases toward negative events. There is substantial theoretical support for the hypothesis that MDD patients overweight potential losses compared with gains, though the neurobiological underpinnings of this bias are uncertain., Methods: Twenty-one unmedicated patients with MDD were compared with 25 healthy controls (HC) using functional magnetic resonance imaging (fMRI) together with an economic decision-making task over mixed lotteries involving probabilistic gains and losses. Region-of-interest analyses evaluated neural signatures of gain and loss coding within a core network of brain areas known to be involved in valuation (anterior insula, caudate nucleus, ventromedial prefrontal cortex)., Results: Usable fMRI data were available for 19 MDD and 23 HC subjects. Anterior insula signal showed negative coding of losses (gain > loss) in HC subjects consistent with previous findings, whereas MDD subjects demonstrated significant reversals in these associations (loss > gain). Moreover, depression severity further enhanced the positive coding of losses in anterior insula, ventromedial prefrontal cortex, and caudate nucleus. The hyper-responsivity to losses displayed by the anterior insula of MDD patients was paralleled by a reduced influence of gain, but not loss, stake size on choice latencies., Conclusions: Patients with MDD demonstrate a significant shift from negative to positive coding of losses in the anterior insula, revealing the importance of this structure in value-based decision-making in the context of emotional disturbances.

Background: Females are more likely than males to develop major depressive disorder (MDD). The current study used fMRI to compare the neural correlates of autobiographical memory (AM) recall between males and females diagnosed with MDD. AM overgenerality is a persistent cognitive deficit in MDD, the magnitude of which is correlated with depressive severity only in females. Delineating the neurobiological correlates of this deficit may elucidate the nature of sex-differences in the diathesis for developing MDD., Methods: Participants included unmedicated males and females diagnosed with MDD (n = 20/group), and an age and sex matched healthy control group. AM recall in response to positive, negative, and neutral cue words was compared with a semantic memory task., Results: The behavioral properties of AMs did not differ between MDD males and females. In contrast, main effects of sex on cerebral hemodynamic activity were observed in left dorsolateral prefrontal cortex and parahippocampal gyrus during recall of positive specific memories, and middle prefrontal cortex (mPFC), and precuneus during recall of negative specific memories. Moreover, main effects of diagnosis on regional hemodynamic activity were observed in left ventrolateral prefrontal cortex and mPFC during positive specific memory recall, and dorsal anterior cingulate cortex during negative specific memory recall. Sex × diagnosis interactions were evident in the dorsomedial prefrontal cortex, caudate, and precuneus during positive memory recall, and in the posterior cingulate cortex, insula, precuneus and thalamus during negative specific memory recall., Conclusions: The differential hemodynamic changes conceivably may reflect sex-specific cognitive strategies during recall of AMs irrespective of the phenomenological properties of those memories.

Background: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share abnormalities in hot executive functions such as reward-based decision-making, as measured in the temporal discounting task (TD). No studies, however, have directly compared these disorders to investigate common/distinct neural profiles underlying such abnormalities. We wanted to test whether reward-based decision-making is a shared transdiagnostic feature of both disorders with similar neurofunctional substrates or whether it is a shared phenotype with disorder-differential neurofunctional underpinnings., Methods: Age and IQ-matched boys with ASD (N = 20), with OCD (N = 20) and 20 healthy controls, performed an individually-adjusted functional magnetic resonance imaging (fMRI) TD task. Brain activation and performance were compared between groups., Results: Boys with ASD showed greater choice-impulsivity than OCD and control boys. Whole-brain between-group comparison revealed shared reductions in ASD and OCD relative to control boys for delayed-immediate choices in right ventromedial/lateral orbitofrontal cortex extending into medial/inferior prefrontal cortex, and in cerebellum, posterior cingulate and precuneus. For immediate-delayed choices, patients relative to controls showed reduced activation in anterior cingulate/ventromedial prefrontal cortex reaching into left caudate, which, at a trend level, was more decreased in ASD than OCD patients, and in bilateral temporal and inferior parietal regions., Conclusions: This first fMRI comparison between youth with ASD and with OCD, using a reward-based decision-making task, shows predominantly shared neurofunctional abnormalities during TD in key ventromedial, orbital- and inferior fronto-striatal, temporo-parietal and cerebellar regions of temporal foresight and reward processing, suggesting trans-diagnostic neurofunctional deficits.

Background: Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are co-morbid and associated with similar neural disruptions during emotion regulation. In contrast, the lack of optimism examined here may be specific to GAD and could prove an important biomarker for that disorder., Method: Unmedicated individuals with GAD (n = 18) and age-, intelligence quotient- and gender-matched SAD (n = 18) and healthy (n = 18) comparison individuals were scanned while contemplating likelihoods of high- and low-impact negative (e.g. heart attack; heartburn) or positive (e.g. winning lottery; hug) events occurring to themselves in the future., Results: As expected, healthy subjects showed significant optimistic bias (OB); they considered themselves significantly less likely to experience future negative but significantly more likely to experience future positive events relative to others (p < 0.001). This was also seen in SAD, albeit at trend level for positive events (p < 0.001 and p < 0.10, respectively). However, GAD patients showed no OB for positive events (t 17 = 0.82, n.s.) and showed significantly reduced neural modulation relative to the two other groups of regions including the medial prefrontal cortex (mPFC) and caudate to these events (p < 0.001 for all). The GAD group further differed from the other groups by showing increased neural responses to low-impact events in regions including the rostral mPFC (p < 0.05 for both)., Conclusions: The neural dysfunction identified here may represent a unique feature associated with reduced optimism and increased worry about everyday events in GAD. Consistent with this possibility, patients with SAD did not show such dysfunction. Future studies should consider if this dysfunction represents a biomarker for GAD.

Background: Under 'cocktail party' listening conditions, healthy listeners and listeners with schizophrenia can use temporally pre-presented auditory speech-priming (ASP) stimuli to improve target-speech recognition, even though listeners with schizophrenia are more vulnerable to informational speech masking., Method: Using functional magnetic resonance imaging, this study searched for both brain substrates underlying the unmasking effect of ASP in 16 healthy controls and 22 patients with schizophrenia, and brain substrates underlying schizophrenia-related speech-recognition deficits under speech-masking conditions., Results: In both controls and patients, introducing the ASP condition (against the auditory non-speech-priming condition) not only activated the left superior temporal gyrus (STG) and left posterior middle temporal gyrus (pMTG), but also enhanced functional connectivity of the left STG/pMTG with the left caudate. It also enhanced functional connectivity of the left STG/pMTG with the left pars triangularis of the inferior frontal gyrus (TriIFG) in controls and that with the left Rolandic operculum in patients. The strength of functional connectivity between the left STG and left TriIFG was correlated with target-speech recognition under the speech-masking condition in both controls and patients, but reduced in patients., Conclusions: The left STG/pMTG and their ASP-related functional connectivity with both the left caudate and some frontal regions (the left TriIFG in healthy listeners and the left Rolandic operculum in listeners with schizophrenia) are involved in the unmasking effect of ASP, possibly through facilitating the following processes: masker-signal inhibition, target-speech encoding, and speech production. The schizophrenia-related reduction of functional connectivity between the left STG and left TriIFG augments the vulnerability of speech recognition to speech masking.

Background Auditory verbal hallucinations (AVHs) have been associated with deficits in auditory and speech-related networks. However, the resting-state cerebral blood flow (CBF) alterations specific to AVHs in schizophrenia remain unknown. Aims To explore AVH-related CBF alterations in individuals with schizophrenia. Method In total, 35 individuals with schizophrenia with AVHs, 41 individuals with schizophrenia without AVHs and 50 controls underwent arterial spin labelling magnetic resonance imaging. The CBF differences were voxel-wise compared across the three groups. Results We found AVH-specific CBF increase in the right superior temporal gyrus and caudate, and AVH-specific CBF decrease in the bilateral occipital and left parietal cortices. We also observed consistent CBF changes in both schizophrenia subgroups (i.e. those with and without AVHs) including decreased CBF in the bilateral occipital regions, the left lateral prefrontal and insular cortices, and the right anterior cingulate cortex and increased CBF in the bilateral lateral temporal regions and putamen, the left middle cingulate cortex and the right thalamus. Conclusions The AVH-specific CBF increases in the auditory and striatal areas and CBF reductions in the visual and parietal areas suggest that there exists a CBF redistribution associated with AVHs., (© The Royal College of Psychiatrists 2017.)

Background: The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment., Method: Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement., Results: Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint., Conclusions: This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.

Background: Obsessive compulsive disorder (OCD) and social anxiety disorder (SAD) are characterized by biased perception and processing of potentially threatening stimuli. A hyper-reactivity of the fear-circuit [e.g. amygdala, anterior cingulate (ACC)] has been consistently reported using functional magnetic resonance imaging (fMRI) in SAD in comparison with healthy controls (HCs). Studies investigating the processing of specific emotional stimuli in OCD reported mainly orbitofrontal-striatal abnormalities. The goal of this study was to examine similar/common and differential neurobiological responses in OCD and SAD using unspecific emotional stimuli., Method: Fifty-four subjects participated: two groups (each n = 18) of outpatients with a current diagnosis of OCD or SAD, and 18 HCs. All subjects underwent fMRI while anticipating and perceiving unspecific visual stimuli with prior announced emotional valence (e.g. positive)., Results: Compared to HCs, the combined patient group showed increased activation in amygdala, caudate and prefrontal/orbitofrontal cortex while anticipating unspecific emotional stimuli. Caudate was more active in the combined patient group during perception. A comparison between the OCD and the SAD samples revealed increased amygdala and decreased rostral ACC activation in OCD patients during perception, but no differences in the anticipation phase., Conclusions: Overall, we could identify common fronto-subcortical hyper-reactivity in OCD and SAD while anticipating and perceiving unspecific emotional stimuli. While differential neurobiological responses between OCD and SAD when processing specific stimuli are evident from the literature, differences were less pronounced using unspecific stimuli. This could indicate a disturbance of emotion regulation common to both OCD and SAD.

Background: There is evidence of executive function impairment in obsessive compulsive disorder (OCD) that potentially contributes to symptom development and maintenance. Nevertheless, the precise nature of these executive impairments and their neural basis remains to be defined., Method: We compared stopping and shifting, two key executive functions previously implicated in OCD, in the same task using functional magnetic resonance imaging, in patients with virtually no co-morbidities and age-, verbal IQ- and gender-matched healthy volunteers. The combined task allowed direct comparison of neural activity in stopping and shifting independent of patient sample characteristics and state variables such as arousal, learning, or current symptom expression., Results: Both OCD patients and controls exhibited right inferior frontal cortex activation during stopping, and left inferior parietal cortex activation during shifting. However, widespread under-activation across frontal-parietal areas was found in OCD patients compared to controls for shifting but not stopping. Conservative, whole-brain analyses also indicated marked divergent abnormal activation in OCD in the caudate and thalamus for these two cognitive functions, with stopping-related over-activation contrasting with shift-related under-activation., Conclusions: OCD is associated with selective components of executive function, which engage similar common elements of cortico-striatal regions in different abnormal ways. The results implicate altered neural activation of subcortical origin in executive function abnormalities in OCD that are dependent on the precise cognitive and contextual requirements, informing current theories of symptom expression.

Background: Depression is a prevalent disorder that significantly affects the social functioning and interpersonal relationships of individuals. This highlights the need for investigation of the neural mechanisms underlying these social difficulties. Investigation of social exchanges has traditionally been challenging as such interactions are difficult to quantify. Recently, however, neuroeconomic approaches that combine multiplayer behavioural economic paradigms and neuroimaging have provided a framework to operationalize and quantify the study of social interactions and the associated neural substrates., Method: We investigated brain activation using functional magnetic resonance imaging (fMRI) in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic paradigm, the Ultimatum Game (UG). In this task, participants accept or reject monetary offers from other players., Results: In comparison to controls, depressed participants reported decreased levels of happiness in response to 'fair' offers. With increasing fairness of offers, controls activated the nucleus accumbens and the dorsal caudate, regions that have been reported to process social information and responses to rewards. By contrast, participants with depression failed to activate these regions with increasing fairness, with the lack of nucleus accumbens activation correlating with increased anhedonia symptoms. Depressed participants also showed a diminished response to increasing unfairness of offers in the medial occipital lobe., Conclusions: Our findings suggest that depressed individuals differ from healthy controls in the neural substrates involved with processing social information. In depression, the nucleus accumbens and dorsal caudate may underlie abnormalities in processing information linked to the fairness and rewarding aspects of other people's decisions.

Background: A substantial proportion of schizophrenia patients also meets DSM-IV criteria for obsessive-compulsive disorder (OCD). Schizophrenia with OCD ("schizo-obsessive") patients are characterized by distinct clinical characteristics, treatment response and prognosis. Whether schizo-obsessive patients exhibit a distinct pattern of brain activation is yet unknown. To address this question, the present functional magnetic resonance imaging (fMRI) study explicitly compared alterations in brain activation and functional connectivity (FC) underlying a working memory deficit in schizophrenia patients with and without OCD., Methods: fMRI was applied during the N-back working memory (WM) task in three groups: schizo-obsessive (n=16), schizophrenia (n=17) and matched healthy volunteers (n=20). WM-related activation in the right dorsolateral prefrontal cortex (DLPFC) and the right caudate nucleus, brain areas relevant to schizophrenia and OCD, and FC analysis were used for the evaluation., Results: The two schizophrenia groups with and without OCD exhibited a similar reduction in activation in the right DLPFC and right caudate, as well as decreased FC compared to the healthy controls. Notably, reduced regional brain activation was not related to severity of schizophrenic or OCD symptoms., Conclusions: Schizo-obsessive patients do not differ from their non-OCD schizophrenia counterparts in brain activation patterns during the N-back WM task. Cognitive paradigms taping alternative neural networks (e.g., orbitofrontal cortex) particularly relevant to OCD, are warranted in the search for potential distinctive brain activation patterns of the schizo-obsessive subgroup., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Huntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals. Participants were genetically confirmed individuals with prodromal HD enrolled in the PREDICT-HD study. Cognitive reserve was computed as the composite of performance on a lexical task estimating premorbid intellectual level, occupational status, and years of education. Linear mixed effects regression (LMER) was used to examine longitudinal changes on four cognitive measures and three brain volumes over approximately 6 years. Higher cognitive reserve was significantly associated with a slower rate of change on one cognitive measure (Trail Making Test, Part B) and slower rate of volume loss in two brain structures (caudate, putamen) for those estimated to be closest to motor disease onset. This relationship was not observed among those estimated to be further from motor disease onset. Our findings demonstrate a relationship between cognitive reserve and both a measure of executive functioning and integrity of certain brain structures in prodromal HD individuals.

Background: Depression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally diverse subregions of the rostral cingulate cortex. Method Eighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups., Results: The depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally., Conclusions: The results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect; and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.

Background: Cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) is the psychotherapeutic treatment of choice for obsessive-compulsive disorder (OCD). However, little is known about the impact of CBT on frontostriatal dysfunctioning, known to be the neuronal correlate of OCD., Method: A probabilistic reversal learning (RL) task probing adaptive strategy switching capabilities was used in 10 unmedicated patients with OCD and 10 healthy controls during an event-related functional magnetic resonance imaging (fMRI) experiment. Patients were scanned before and after intensive CBT, controls twice at comparable intervals., Results: Strategy change within the RL task involved activity in a broad frontal network in patients and controls. No significant differences between the groups or in group by time interactions were detected in a whole-brain analysis corrected for multiple comparisons. However, a reanalysis with a more lenient threshold revealed decreased responsiveness of the orbitofrontal cortex and right putamen during strategy change before treatment in patients compared with healthy subjects. A group by time effect was found in the caudate nucleus, demonstrating increased activity for patients over the course of time. Patients with greater clinical improvement, reflected by greater reductions in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, showed more stable activation in the pallidum., Conclusions: Although these findings are preliminary and need to be replicated in larger samples, they indicate a possible influence of psychotherapy on brain activity in core regions that have been shown to be directly involved both in acquisition of behavioral rules and stereotypes and in the pathophysiology of OCD, the caudate nucleus and the pallidum.

As a result of clinical, epidemiological, neuroimaging, and therapy studies that took place in the late 1980s, obsessive-compulsive disorder (OCD) has been well-characterized in the field of anxiety disorders. Other disorders attracted attention for their similarities to OCD, and were located in the orbit of the disorder. OCD has become known as the "primary domain" of a scientific "metaphor" comprising the putative cluster of OCD-related disorders (OCRDs). It is a "paradigm" with which to explore basal ganglia dysfunction. The OCRDs share common phenomenology, comorbidities, lifetime course, demographics, possible genetics, and frontostriatal dysfunction (particularly caudate hyperactivity.) The adoption of this metaphor analogy has proven useful. However, 15 years since its emergence, the spectrum of obsessive-compulsive disorders remains controversial. Questions under debate include whether OCD is a unitary or split condition, whether it is an anxiety disorder, and whether there exists only one spectrum or several possible spectrums. Further work is needed to clarify obsessive-compulsive symptoms, subtypes, and endophenotypes. There is need to integrate existing databases, better define associated symptom domains, and create a more comprehensive endophenotyping protocol for OCRDs. There is also a need to integrate biological and psychological perspectives, concepts, and data to drive this evolution. By increasing research in this field, the OCD spectrum may evolve from a fragmented level of conceptualization as a "metaphor" to one that is more comprehensive and structured.

Production of complex discourse-lengthy, open-ended utterances and narratives-requires intact basic language operations, but it also requires a series of learned procedures for construction of complex, goal-directed communications. The progression of clinical disorders from transcortical motor aphasia to dynamic aphasia to discourse impairments represents a progression of procedural deficits from basic morpho-syntax to complex grammatical structures to narrative and a progression of lesions from posterior frontal to polar and/or lateral frontal to medial frontal. Two cases of impaired utilization of language exemplify the range of impairments from clearly aphasic agrammatic, nonfluency to less and less "aphasic" and more and more executive impairments from transcortical motor aphasia to dynamic aphasia to narrative discourse disorder. The clinical phenomenology of these disorders gradually comes to be more accurately defined in the terminology of executive deficits than that of aphasia. The executive deficits are, in turn, based on impairments in various components of attention. Specific impairments in energizing attention and setting response criteria associated, respectively, with lesions in superior medial and left ventrolateral frontal regions may cause defective recruitment of the procedures of complex language assembly.

Fifty-three volunteer participants were studied with the fade-in task (Ostergaard, 1998) to measure naming latency, word priming, and recognition-memory performance. and with morphometric magnetic resonance imaging (MRI) techniques to measure volumes of mesial temporal lobe, diencephalic, striatal, and neocortical structures. The relationship between measures of cerebral volume loss and performance deficits was modeled using simultaneous regression analyses in which the behavioral measures were dependent variables. The results suggested that damage in both hippocampal and amygdala/entorhinal areas as well as damage in the diencephalon and the nucleus accumbens all contributed independently to the severity of recognition-memory deficits. Both caudate nucleus damage and hippocampal damage contributed independently to increased naming latency (slowed single-word reading). Finally, only damage in the hippocampus appeared to result in decreased word priming. These results provide further evidence against the assertion that word priming represents a form of memory unaffected by damage to the mesial temporal lobes.

Background: A 67-year-old man presented with acute onset of spatial and temporal disorientation, memory loss and associated episodic dyscontrol. Investigations showed infarctions of both caudate nuclei. This patient presented a unique opportunity to study the relationship between the lesions, his behaviour, and neuropsychological testing., Method: Single case report. Investigations included interviews to determine cognitive impairment, i.e. WAIS-R, MMSE, and neurological examination., Results: Extensive neuropsychological testing revealed severe impairment on tasks requiring planning, memory or abstract thought. These findings are very similar to those seen in Huntington's disease., Conclusions: A neurobiological hypothesis is proposed to account for his symptoms, and recent discoveries in the basic sciences used to inform his management.

This study describes a cohort of 23 patients undergoing stereotactic subcaudate tractotomy. Research Diagnostic Criteria indicated that 70% suffered major depressive disorder; the remainder mostly had a bipolar affective disorder. There were serial assessments pre-operatively and at 2 weeks and 6 months post-operatively using the Hamilton Rating Scale for depression, the Present State Examination (PSE), Newcastle Scale, the Beck Depression Inventory, and the Taylor Manifest Anxiety Scale. Neuropsychological assessment included tests thought to be sensitive to frontal lobe dysfunction, as well as tests of general intelligence, attention, memory, language and visuo-spatial function. Post-operatively, depression rating scale scores decreased significantly but most patients continued to exhibit a number of PSE syndromes. Depression rating scale scores were correlated with 1 year global outcome: there was no significant correlation except for the 6 month assessment when lower Hamilton scores were found to be associated with better global outcome. Correlations between the neuropsychological tests and the Hamilton and Beck depression scales at 2 weeks post-operatively suggested that an improvement in psychiatric condition was associated with greater efficiency on some tests of attention and verbal recall, as well as faster performance on a sorting task. By contrast, the changes at 6 months suggested an association between improvement in psychiatric condition and less efficient performance on certain neuropsychological tests including verbal recognition memory, attention and two tests of frontal lobe dysfunction.

Background: Stereotactic subcaudate tractotomy (SST) is the only type of psychosurgery performed at the Geoffrey Knight Unit, London, where nearly 1300 operations have been done since 1961. Statistically reliable data are not available to prove the effectiveness of SST. A detailed statement about contemporary psychosurgery is given., Method: Relevant publications from the Unit and via Medline are discussed. The outcome figures are reviewed. The outcome is assessed at the Unit in global and clinical terms, associated with results of self-completed questionnaires., Results: SST allows 40-60% of patients to live normal or near-normal lives, perhaps with continuation of medication. A reduction in suicide rate to 1% post-operatively, from 15% in cases of uncontrolled affective disorders is seen., Conclusion: As a treatment of last resort, no controlled trial against a comparable treatment is possible. It appears reasonable to offer SST to patients with suicidal and deluded depression or with frequently swinging moods, not responding to other treatments.

Samples of ventricular CSF were taken from 52 consecutive patients admitted for psychosurgery for intractable depression. Concentrations of asparagine, aspartate, glutamine, glutamic acid, and serine were determined. Glutamate and aspartate concentrations, implicated in excitotoxic brain damage, were not affected by various types of psychotropic drug treatment. Serine, a modulator of glutamate responses, was significantly elevated in samples from subjects receiving antidepressants. These subjects responded poorly to the operation. Psychotropic drugs are unlikely to be neurotoxic. Nevertheless, antidepressants may influence excitatory neurotransmission.