Search results

Future directions for brain health clinics.

Brain Health Services are second-generation memory clinics that aim to reduce the risk of progression to dementia in at-risk individuals. We describe the rationale for such a service, and comment on its novel implementation by Venkataraman and colleagues that integrates digital technologies and biomarker testing. We describe the advantages and possible limitations of such an approach, then investigate areas for further work - namely, the need to account for multiple pathologies in biomarker testing and to formulate standards for genetic counselling.

COVID-19 and substance use disorders: a review of international guidelines for frontline healthcare workers of addiction services.

BACKGROUND: People with substance use disorders may be at a greater risk of contracting COVID-19 infection and developing medical complications. Several institutional and governmental health agencies across the world developed ad hoc guidance for substance use disorder services and care of individuals misusing substances. We aimed to synthesise the best available recommendations on management and care of people with or at risk of substance use disorders during the COVID-19 pandemic from existing guidelines published in UK, USA, Australia, Canada, New Zealand, and Singapore. METHODS: We systematically searched existing guidelines and websites from 28 international institutions and governmental bodies in the context of the COVID-19 pandemic (May 4th 2021). We summarized the extracted data as answers to specific clinical questions. RESULTS: We organised the available recommendations from 19 sources in three sections. First, we focused on general advice and recommendations for people who misuse alcohol or drugs during the COVID-19 pandemic, the design of contingency plans, safeguarding issues for children and families of service users and advice to the public, patients, and carers. Then, we summarised specific guidelines for people who use illicit drugs and related services, such as opioid substitution treatment and needle and syringe programmes. Finally, we provided a synthesis on specific recommendations for services supporting people who misuse alcohol and key topics in the field, such as management of alcohol detoxification and safe transition between supervised and unsupervised consumption. CONCLUSIONS: Available guidance reflected different approaches, ranging from being extremely cautious in providing recommendations other than generic statements to proposing adaptation of previously available guidelines to confront the challenges of the COVID-19 pandemic. After the early phase, guidance focused on reduction of infection transmission and service delivery. Guidance did not provide advice on infection prevention via vaccination programmes and service access strategies tailored to individuals with substance use disorders.

Neural dynamics of reselecting visual and motor contents in working memory after external interference.

In everyday tasks, we must often shift our focus away from internal representations held in working memory to engage with perceptual events in the external world. Here, we investigated how our internal focus is reestablished following an interrupting task by tracking the reselection of visual representations and their associated action plans in working memory. Specifically, we ask whether reselection occurs for both visual and motor memory attributes and when this reselection occurs. We developed a visual-motor working-memory task in which participants were retrospectively cued to select one of two memory items before being interrupted by a perceptual discrimination task. To determine what information was reselected, the memory items had distinct visual and motor attributes. To determine when internal representations were reselected, the interrupting task was presented at one of three distinct time points following the retro-cue. We employed electroencephalography time-frequency analyses to track the initial selection and later reselection of visual and motor representations, as operationalized through modulations of posterior alpha (8-12 Hz) activity relative to the memorized item location (visual) and of central beta (13-30 Hz) activity relative to the required response hand (motor). Our results showed that internal visual and motor contents were concurrently reselected immediately after completing the interrupting task, rather than only when internal information was required for memory-guided behavior. Thus, following interruption, we swiftly resume our internal focus in working memory through the simultaneous reselection of memorized visual representations and their associated action plans, thereby restoring internal contents to a ready-to-use state.Significance statement A key challenge for working memory is to maintain past visual representations and their associated actions while engaging with the external environment. Our cognitive system must, therefore, often juggle multiple tasks within a common time frame. Despite the ubiquity of multi-task situations in everyday life, working memory has predominantly been studied devoid of additional perceptual, attentional, and response demands during the retention interval. Here, we investigate the neural dynamics of returning to internal contents following task-relevant interruptions. Particularly, we identify which attributes of internal representations are reselected and when this reselection occurs. Our findings demonstrate that both visual and motor contents are reselected immediately and in tandem after completion of an external, interrupting task.

A Systematic Review of Guided, Parent-Led Digital Interventions for Preadolescent Children with Emotional and Behavioural Problems

Abstract Emotional and behavioural problems (EBP) are prevalent amongst children, and guided, parent-led digital interventions offer one method of improving access to effective treatments. This systematic review (PROSPERO: CRD42023484098) aimed to examine the evidence base for, and characteristics of, these types of interventions through a narrative synthesis. Systematic searches were conducted using Medline, EMBASE, PsycINFO, Scopus and Web of Science in January 2024 and February 2025, supplemented with hand searching in March/April 2024 and February 2025. Studies were eligible if they reported outcomes related to preadolescent EBP from a guided, fully parent-led, fully digital intervention. Thirteen studies were eligible, including 2643 children and covering eight interventions (addressing anxiety problems, comorbid anxiety and depression, attention deficit hyperactivity disorder, conduct disorder and disruptive behaviour). Studies included randomised controlled trials and pre-post studies. The QualSyst checklist was used to assess study quality; all studies were rated as good quality. All studies showed statistically significant improvements in the child’s symptoms or interference levels, with small to very large effect sizes immediately post-treatment, and at least medium effect sizes by follow-up, suggesting a promising evidence base. A wide range of intervention characteristics were identified, forming a basis for future intervention development for childhood EBP. However, there was a lack of consistency in how information was reported across studies (such as completion rates) and studies lacked information on parent demographics and key intervention details. Further high quality randomised controlled trials for a wider range of EBP are needed to continue building the evidence base.

A single dose of lamotrigine induces a positive memory bias in healthy volunteers.

BACKGROUND: Lamotrigine has been shown to be effective in the long-term treatment and relapse prevention of depression in bipolar disorder. However, the neuropsychological mechanisms underlying these effects are unclear. We investigated the effects of lamotrigine on a battery of emotional processing tasks in healthy volunteers, previously shown to be sensitive to antidepressant drug action in similar experimental designs. METHODS: Healthy volunteers (n = 36) were randomized in a double-blind design to receive a single dose of placebo or 300 mg lamotrigine. Mood and subjective effects were monitored throughout the study period, and emotional processing was assessed using the Oxford Emotional Test Battery (ETB) 3 hours post-administration. RESULTS: Participants receiving lamotrigine showed increased accurate recall of positive versus negative self-descriptors, compared to those in the placebo group. There were no other significant effects on emotional processing in the ETB, and lamotrigine did not affect ratings of mood or subjective experience. CONCLUSIONS: Lamotrigine did not induce widespread changes in emotional processing. However, there was increased positive bias in emotional memory, similar to the effects of antidepressants reported in previous studies. Further work is needed to assess whether similar effects are seen in the clinical treatment of patients with bipolar disorder and the extent to which this is associated with its clinical action in relapse prevention.

Neurophysiological progression in Alzheimer's disease: insights from dynamic causal modelling of longitudinal magnetoencephalography

The impact of personality traits on the return of major depression: a case-control study.

BACKGROUND: Major depression is a common, chronic, recurrent, debilitating disorder. Despite effective treatments, remission rates remain low, and many of those who do experience remission then relapse. Some personality traits are potential risk factors for relapse, though they have, to date, received insufficient attention. There is growing attention to the role of emotional dysregulation in recurrent depression. We aimed to investigate the association between the return of major depression and emotional dysregulation, affective lability, and impulsivity personality traits. METHOD: A case-control design sampling adults over 18 years old with a history of depression and currently either experiencing a depressive episode (cases) or currently being free of a depressive episode (controls). Current depression was assessed using the Patient Health Questionnaire-9, and study participants were recruited online. Multi-staged logistic regression modelling was used to explore the association between personality traits and the return of depression, adjusting for important confounding factors. RESULTS: One hundred fifty two respondents (76 cases and 76 controls) were recruited. Emotional dysregulation was significantly associated with the return of depression (OR = 1.03, 95% CI [1.00-1.06], p = 0.04) even after adjustment for the confounding factors: marital status and childhood trauma. Childhood trauma (OR = 1.04, 95% CI [1.00-1.08], p = 0.03) and being widowed, divorced, or separated (OR = 13.95, 95% CI [1.16-166], p = 0.03) were also associated with the return of depression. Our analysis did not detect any association between affective lability and impulsivity and the return of depression. LIMITATIONS: Our study relied on self-report questionnaires, including measuring depression. We used cross-sectional data in the present study analysis. CONCLUSION: Our findings suggest emotional dysregulation and childhood trauma could work as risk factors and predate depression. This information can be used to develop targeted treatment plans and improve therapeutic outcomes.

Current and prospective roles of magnetic resonance imaging in mild traumatic brain injury

There is unmet clinical need for biomarkers to predict recovery or the development of long-term sequelae of mild traumatic brain injury, a highly prevalent condition causing a constellation of disabling symptoms. A substantial proportion of patients live with long-lasting sequelae affecting their quality of life and ability to work. At present, symptoms can be assessed through clinical tests; however, there are no imaging or laboratory tests fully reflective of pathophysiology routinely used by clinicians to characterize post-concussive symptoms. Magnetic resonance imaging has potential to link subtle pathophysiological alterations to clinical outcomes. Here, we review the state of the art of MRI research in adults with mild traumatic brain injury and provide recommendations to facilitate transition into clinical practice. Studies utilizing MRI can inform on pathophysiology of mild traumatic brain injury. They suggest presence of early cytotoxic and vasogenic oedema. They also show that mild traumatic brain injury results in cellular injury and microbleeds affecting the integrity of myelin and white matter tracts, all processes that appear to induce delayed vascular reactions and functional changes. Crucially, correlates between MRI parameters and post-concussive symptoms are emerging. Clinical sequences such as T1-weighted MRI, susceptibility-weighted MRI or fluid attenuation inversion recovery could be easily implementable in clinical practice, but are not sufficient, in isolation for prognostication. Diffusion sequences have shown promises and, although in need of analysis standardization, are a research priority. Lastly, arterial spin labelling is emerging as a high-utility research as it could become useful to assess delayed neurovascular response and possible long-term symptoms.

Focusing attention in working and long-term memory through dissociable mechanisms.

We developed an experimental approach to compare how attentional orienting facilitates retrieval from spatial working memory (WM) and long-term memory (LTM), and how selective attention within these two memory types impacts incoming sensory information processing. In three experiments with healthy young adults, retrospective attention cues prioritize an item represented in WM or LTM. Participants then retrieve a memory item or perform a perceptual task. The retrocue is informative for the retrieval task but not for the perceptual task. We show that attentional orienting benefits performance for both WM and LTM, with stronger effects for WM. Eye-tracking reveals significant gaze shifts and microsaccades correlated with attention in WM, but no statistically significant gaze biases were found for LTM. Visual discrimination of unrelated visual stimuli is consistently improved for items matching attended WM locations. Similar effects occur at LTM locations but less consistently. The findings suggest at least partly dissociable attention-orienting processes for different memory types. Although our conclusions are necessarily constrained to the type of WM and LTM representations relevant to our task, they suggest that, under certain conditions, attentional prioritization in LTM can operate independently from WM. Future research should explore whether similar dissociations extend to non-spatial or more complex forms of LTM.

Explaining and understanding in psychopathology.

Psychoanalytical methodology has been described as causal explanation or hermeneutic understanding. This methodological dichotomy has been introduced into psychopathology by Karl Jaspers. Contemporary authors' contributions in the area are discussed. Although these authors accept a role for both methods, they agree with Jaspers that psychoanalysis should be subjected to the logical limitations of hermeneutic analysis. A logical framework for the interaction of explaining with understanding is presented and discussed in relation to psychiatric research.

Further evidence that reading ability is not preserved in Alzheimer's disease.

BACKGROUND: Pre-morbid intelligence level is routinely assessed in Alzheimer's disease using the National Adult Reading Test (NART). This practice is based on the assumption that pronunciation of irregular words remains unaffected by the disease process. Recent reports have suggested that reading ability may become compromised in moderately demented subjects. METHOD: Sixty-eight probably Alzheimer patients were classified into stages of severity (minimal, mild and moderate) using the Mini-Mental State Examination (MMSE). NART and demographic equations were used to estimate pre-morbid ability. RESULTS: A significant correlation emerged between dementia severity and reading ability, NART v. MMSE scores, r = 0.46, P < 0.01. When the total sample was subdivided into moderate, mild and minimal subgroups, significant between-group differences emerged, despite the groups being well matched for age, sex, and years of full-time education. Pre-morbid IQ, as estimated by demographic regression equations, did not correlate with dementia severity. CONCLUSION: NART performance is compromised in moderate Alzheimer disease, and the measure provides a serious underestimate of pre-morbid IQ in patients with an MMSE of 13 or less.

Follow-up study of depression in the elderly. Clinical and SPECT data.

BACKGROUND: Imaging studies in depression of the elderly are often small and highly selective. AIMS: To investigate a large group of elderly depressed patients in order to assess changes in clinical, imaging and neuropsychological variables at follow-up. METHOD: Patients (n = 175, age range 65-91 years) with clinical depression were identified from consecutive local referrals. Clinical interviews, neuropsychological tests and SPECT scans were carried out at referral and at two-year follow-up. RESULTS: Of 84 re-examined patients, 46.5% were well, 9.5% were ill, 33% partially recovered and 11% had developed dementia. Duration of illness before index assessment was the only factor to predict outcome. Thirty-nine patients could be scanned and followed up. There were no differences between patients with good or poor depressive outcome on SPECT. Ten clinically improved patients could be re-examined with SPECT. There were relative increases in right cingulate gyrus and right cerebellum at follow-up. CONCLUSIONS: The patients group was comparable with other studies showing high levels of residual depressive symptoms. Activity changes in limbic cortex are implicated in depression of old age.

Brain imaging and treatment response in spasmodic torticollis.

A patient with spasms of the neck, occurring when he turned his head to the left, responded to treatment with benzhexol. Cerebral blood flow imaging demonstrated reduced uptake in the right corpus striatum compared with the left. The study demonstrates the presence of an abnormality in the basal ganglia; it also illustrates response to drug treatment. Cerebral blood flow imaging may be useful in the detection of basal ganglia abnormalities in spasmodic torticollis and assist in the selection of cases which should be targeted for treatment with drugs.

Magnetic resonance imaging and single photon emission tomography in treatment-responsive and treatment-resistant schizophrenia.

BACKGROUND: Patients with schizophrenia differ from controls in several measures of brain structure and function, but it is uncertain how these relate to clinical features of the illness. We dichotomised patient groups by treatment response to test the hypothesis that treatment-resistant patients exhibit more marked biological abnormalities than treatment-responsive patients. METHOD: Twenty treatment-responsive and 20 treatment-resistant patients with schizophrenia, matched for sex, age, and illness duration, were compared by magnetic resonance imaging, single photon emission tomography, and detailed neuropsychological assessment. RESULTS: Brain-imaging variables were not statistically related to treatment response, although poorly responsive patients had lower volumes of most brain structures. Several highly significant differences emerged between patient groups on neuropsychological testing. Episodic memory functioning distinguished patient groups even after we controlled for global cognitive impairment. CONCLUSIONS: Cerebral structure and blood flow have a limited effect on treatment response in schizophrenia, but long-term episodic memory impairment is associated with, and may predict, poor prognosis.

A single photon emission computerised tomography study of regional brain function underlying verbal memory in patients with Alzheimer-type dementia.

Ten patients with Alzheimer-type dementia and nine age-matched normal controls were examined with SPECT, using split-dose 99mTc-labelled exametazime. The baseline condition involved repetition of the word 'yes' or 'no'. The activation condition involved recognition (indicated by a 'yes' or 'no') of words from a previously learned list presented along with distractor words. Patients who performed this task successfully were selected, and efforts were made to match the patients with controls according to their performance on the task, although this was not fully achieved. Uptake of 99mTc-exametazime was estimated at baseline and during the word-recognition task for predetermined regions of interest drawn from a standard neuroanatomical atlas. The baseline task appeared to normalise tracer uptake for frontal, temporal and parietal cortex in the patient group. However, during the recognition task, controls but not patients showed activation effects. These were most prominent in dorsolateral frontal cortex and adjacent anterior cingulate cortex. Among patients, successful performance was correlated with activation of dorsolateral frontal and parietal cortex on the left side. The results confirm the central role of frontal mechanisms in a recognition memory task. The study highlights some of the difficulties of using cognitive challenge tests in clinical groups.

A single photon emission computerised tomography study of regional brain function in elderly patients with major depression and with Alzheimer-type dementia.

The uptake, at rest, of 99mTc-exametazime into different brain regions was compared using SPECT for 20 elderly subjects with major depressive disorder, 20 with Alzheimer-type dementia, and 30 age-matched normal volunteers. Uptake was referred to calcarine-occipital cortex as a reference sensory area. Cross-sectional differences between the three groups were highly statistically significant, but reflected primarily the reductions in cortical uptake in the Alzheimer group. A detailed comparison of depressed patients and controls identified decrements in anterior cingulate, temporal and frontal cortex and in caudate and thalamus in men only. These decrements were correlated with impairment of performance on a trail-making task, but were also associated with continuing treatment with antidepressants or benzodiazepines. However, most depressed patients had quantitatively normal scans for posterior parietal association cortex, and this suggests that SPECT may find a limited role in the differential diagnosis of depression and dementia. The reduced brain function in some depressed patients may parallel the findings from studies of brain structure in elderly depressives; there was between good outcome at 6-18 months and increased tracer uptake in subcortical areas.

Multimodal imaging in Alzheimer's disease. The relationship between MRI, SPECT, cognitive and pathological changes.

Patients with a clinical diagnosis of Alzheimer's disease were studied using MRI, SPECT, and psychometric tests. Significant correlations between focal perfusion deficits and focal cognitive deficits were found. Significant correlations between regional relaxation time of white matter and psychometric tests of diffuse and focal categories were also found. Pathological examination confirmed Alzheimer's disease as the only diagnosis.

The neuropsychiatric sequelae of mercury poisoning. The Mad Hatter's disease revisited.

BACKGROUND: The detailed effects of mercury poisoning on cognitive function, brain anatomy and regional brain function are largely unknown. We report the case of a 38-year-old man who was exposed to toxic levels of inorganic mercury. METHOD: Four years after exposure, the patient was assessed using magnetic resonance imaging (MRI), single-photon emission computerised tomography (SPECT) and detailed neuropsychological evaluation. RESULTS: The patient developed a myriad of physical and psychiatric complaints, including stomatitis, muscle spasm, tremor, skin rash and the psychiatric syndrome known as 'erythism' (Mad Hatter's disease). Neuropsychological evaluation revealed marked and significant deficits of attention concentration, particularly when under time pressure. The MRI scan was unremarkable; however, SPECT revealed hypermetabolism of the posterior cingulate CONCLUSIONS: Mercury poisoning appeared to result in a dysregulation of posterior cingulate cortex, which was associated with attention/concentration deficits and marked anxiety/agitation.

Estimation of premorbid intelligence in schizophrenia.

To determine whether the National Adult Reading Test (NART) would provide a valid estimate of premorbid intelligence in schizophrenia, two schizophrenic samples were recruited, one consisting of 35 patients resident in long-stay wards, the other of 29 patients normally resident in the community. Schizophrenic patients were individually matched for age, sex, and education with a healthy, normal subject. Both schizophrenic samples scored significantly lower on the Wechsler Adult Intelligence Scale (WAIS) than their respective control groups. NART-estimated IQ did not differ significantly between the community-resident schizophrenics and their controls, suggesting that the NART provides a valid means of estimating premorbid intelligence in such a population. NART-estimated IQ was significantly lower in the long-stay sample than in their controls. Although low NART scores in this latter sample could be a valid reflection of low premorbid IQ, the alternative explanation that NART performance was impaired by onset of the disease cannot be ruled out.

Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Controlled magnetic resonance imaging study.

BACKGROUND: The aetiology of treatment-resistant major depression is little understood; its apparent intractability may reflect brain abnormality. METHOD: Magnetic resonance images of the brains of 20 subjects with major depression lasting for two years or more were compared with 20 healthy control subjects and 20 other subjects who had completely recovered from depression. Subjects were individually matched for age, gender, years of education and premorbid IQ. Grey matter was segmented from the images, and compared between groups on a voxel-by-voxel basis. RESULTS: Subjects with chronic depression showed reduced grey matter density in the left temporal cortex including the hippocampus. There was also a trend for reduction in the right hippocampus. Left hippocampal grey matter density was correlated with measures of verbal memory, supporting the functional significance of the observed magnetic resonance imaging changes. CONCLUSIONS: Our results potentially challenge the accepted view of depression as a functional and fully reversible illness, implying instead that more permanent brain changes may be associated with chronicity. Confirmatory longitudinal and prospective studies are required to determine whether these differences pre-date the onset of depression or are the result of the chronic illness process or its treatment.