Tracking longitudinal language network reorganisation using functional MRI connectivity fingerprints.

Large individual differences in how brain networks respond to treatment hinder efforts to personalise treatment in neurological conditions. We used a brain network fingerprinting approach to longitudinally track re-organisation of complementary phonological and semantic language networks in 19 patients before and after brain-tumour surgery. Patient task fingerprints were individually compared to normal networks established in 17 healthy controls. Additionally, pre- and post-operative patient fingerprints were directly compared to assess longitudinal network adaptations. We found that task networks remained stable over time in healthy controls, whereas treatment induced reorganisation in 47.4% of patient fluency networks and 15.8% of semantic networks. How networks adapted after surgery was highly unique; a subset of patients (10%) showed 'normalisation' while others (21%) developed newly atypical networks after treatment. The strongest predictor of adaptation of the fluency network was the presence of clinically reported language symptoms. Our findings indicate a tight coupling between processes disrupting performance and neural network adaptation, the patterns of which appear to be both task- and individually-unique. We propose that connectivity fingerprinting offers potential as a clinical marker to track adaptation of specific functional networks across treatment interventions over time.

Are there distinct forms of accelerated forgetting and, if so, why?

Whether accelerated long-term forgetting (ALF) and classic organic amnesia, particularly hippocampal-amnesia, differ qualitatively or merely quantitatively is disputed. Qualitative difference accounts postulate that ALF patients show normal recall memory for at least minutes, during which hippocampal-amnesics already show accelerated forgetting and impaired recall but, thereafter, ALF patients show accelerated forgetting and impaired delayed recall. These delayed impairments may be more severe than those shown by hippocampal-amnesics. In contrast, quantitative difference accounts postulate that ALF patients merely have mild hippocampal-amnesia, so their later forgetting rates and recall levels are sub-normal but always better than those of hippocampal-amnesics with worse initial recall levels (i.e., there is no cross-over in forgetting rates at longer delays). Many ALF studies in people with epilepsy have demonstrated evidence of a single dissociation-with accelerated delayed forgetting relative to healthy controls. Even when initial recall seems genuinely normal, uncompromised by patients needing more learning trials or showing below-average performance on more demanding recall tests, without further evidence, a quantitative interpretation remains possible. Resolution of the dispute requires evidence of a double dissociation between ALF patients and hippocampal-amnesics with more impaired initial recall in a comparison also involving matched controls. The only two studies that have made this comparison found that there was a cross-over interaction between initial and delayed recall in the ALF and amnesic patients, inconsistent with quantitative difference accounts. The functional and pathological conditions underlying this cross-over effect need to be systematically explored, controlling for potential methodological confounds, in temporal lobe epilepsy and transient epileptic amnesia as well as non-epileptic conditions. Future research must also explore under what conditions, if any, milder hippocampal-amnesics show relatively normal delayed forgetting of recall, and for how long, if at all, ALF patients show completely normal recall. Relatedly, the functional and pathological heterogeneity of ALF needs systematic exploration.

The Relational Impact of Multiple Sclerosis: An Integrative Review of the Literature Using a Cognitive Analytic Framework.

This integrative literature review uses cognitive analytic therapy (CAT) theory to examine the impact of a chronic illness, multiple sclerosis (MS), on relationships and mental health. Electronic searches were conducted in six medical and social science databases. Thirty-eight articles met inclusion criteria, and also satisfied quality criteria. Articles revealed that MS-related demands change care needs and alter relationships. Using a CAT framework, the MS literature was analysed, and five key patterns of relating to oneself and to others were identified. A diagrammatic formulation is proposed that interconnects these patterns with wellbeing and suggests potential "exits" to improve mental health, for example, assisting families to minimise overprotection. Application of CAT analysis to the literature clarifies relational processes that may affect mental health among individuals with MS, which hopefully will inform how services assist in reducing unhelpful patterns and improve coping. Further investigation of the identified patterns is needed.

Clinical Experience with Pedunculopontine Nucleus Stimulation in Conditions with Nigrostriatal Disconnection.

BACKGROUND: The pedunculopontine nucleus (PPN) is a part of the mesencephalic locomotor region and, in recent years, it has been considered a new surgical target for deep brain stimulation (DBS) for movement disorders including atypical parkinsonian syndromes such as progressive supranuclear palsy (PSP) and multiple system atrophy. Involvement of the PPN may play an important role in gait impairment in these disorders and the development of PPN DBS could potentially provide treatment for this disabling problem. However, the role of the PPN and the specific pathways involved in gait control and other motor functions are poorly understood. METHODS: We present a chronological account of our group's experience in the use of PPN DBS. This entails the treatment of four patients with disabling movement disorders who all exhibited either marked damage or disconnection of the nigro-striatal pathway. RESULTS: Within our series, the results were variable in that 2 of the 4 patients benefited greatly from DBS but the other 2 did not. CONCLUSIONS: Our findings suggest that in carefully selected patients, PPN DBS can potentially alleviate symptoms due to dopaminergic striatal inactivity; symptoms that are typically resistant to stimulation of other subcortical targets used for parkinsonian syndromes and movement disorders.

The association between involuntary memory and emotional adjustment after childbirth.

OBJECTIVES: A woman's memory of her experience of giving birth can strongly influence her mental health, and the development of her relationship with her infant, in a positive or negative direction. Highly distressing, involuntary memories of the birth may indicate symptoms of post-traumatic stress (PTS), which is increasingly recognized as a possible outcome of childbirth. Involuntary memories are not, however, exclusive to trauma and can also be experienced after positive events. This study sought to investigate involuntary memories for childbirth, as this is an event that is known to be potentially experienced both as highly positive and negative, and associated with a range of emotional outcomes, including greater well-being and symptoms of PTS. METHODS: A total of 122 women completed a measure of their emotional experience of giving birth within 3 days of the event, and 65 of these women responded to a postal follow-up at 6 weeks, with measures of involuntary memory experience, PTS symptoms and well-being. RESULTS: Experiencing pleasant involuntary memories was more common than experiencing unpleasant involuntary memories of the birth. The frequency of these memories and how they were experienced as either distressing or enjoyable was associated with post-partum emotional adjustment, demonstrated by the development of PTS symptoms or greater well-being. CONCLUSIONS: These results are important because to date, little research has examined the development of positive involuntary memories and their association with positive emotional adjustment. Statement of contribution What is already known on this subject? Positive and negative emotional experiences can coexist in childbirth. Involuntary memories after negative events can be associated with post-traumatic stress. Involuntary memories can also occur after strongly positive events. What does this study add? Women can experience both positive and negative involuntary memories after childbirth. Involuntary negative memories mediate the link between birth experience and post-traumatic stress. Positive involuntary memories are associated with greater well-being in the post-partum. Transformation of negatively experienced events into positively experienced involuntary memories may facilitate adjustment after childbirth.

"Putting one foot in front of the other": a qualitative study of emotional experiences and help-seeking in women with multiple sclerosis.

Treatments for depression and anxiety in multiple sclerosis (MS) are effective but evidence suggests that individuals do not always seek help for emotional difficulties. This study explored how ten women with MS (aged 30-64), recruited via a hospital based MS clinic, coped with and understood their emotions. The semi-structured interviews were analysed using interpretative phenomenological analysis. Eight participants discussed the analytic process and themes. Four overarching themes emerged: Disclosure stress, Uncomfortable dependence, Facing deterioration and One step at a time. The women struggled emotionally with many aspects of living with MS yet coping alone provided a way of defying MS and maintaining independence and control. The women needed emotional support but reported thinking others either did not notice or understand; their emotions often felt invisible. More holistic care from services was desired. Non help-seeking for distress was partially influenced by a desire to keep things "normal" and a lack of knowledge regarding service provision.

Measuring forgetting: a critical review of accelerated long-term forgetting studies.

Accelerated long-term forgetting (ALF) refers to abnormal forgetting over hours to weeks despite normal acquisition or initial consolidation. Since standardised assessments of memory typically only test at delays of up to 40-minutes, ALF may go undetected in clinical practice. The memory difficulties associated with ALF can however cause considerable distress to patients. It is important therefore that clinicians are aware that ALF may represent a distinct phenomenon that will require additional and careful assessment to aid patients' understanding of the condition and assist in developing strategies to address its effects. At the same time, ALF may also provide insight into long-term memory processes. Studies of ALF in patients with epilepsy have so far demonstrated mixed results, which may reflect differences in methodology. This review explores the methodological issues that can affect forgetting, such as the effects of age, general cognitive function, test sensitivity and initial learning. It then evaluates the extent to which existing studies have considered these key issues. We outline the points to consider when designing ALF studies that can be used to help improve their validity. These issues can also help to explain some of the mixed findings in studies of ALF and inform the design of standardised tests for assessing ALF in clinical practice.

Cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Depression is a common symptom in people with multiple sclerosis. We systematically reviewed published controlled trials on the effectiveness of cognitive behavioural therapy (CBT) for the treatment of depression in people with multiple sclerosis. METHODS: Publications were identified using MEDLINE, PsycINFO and the Cochrane Central Register of Controlled Trials to June/July 2013. We combined thesaurus and free-text terms which were synonyms of the concepts multiple sclerosis, depression and cognitive behavioural therapy. We included published controlled trials which compared individual, group CBT, conducted face-to-face or remotely, to no CBT. Two reviewers extracted data to calculate standardized mean differences (SMD) for self-reported symptoms of depression and weighted mean differences (WMD) for the Multiple Sclerosis Impact Scale (MSIS-29), with 95% Confidence Intervals (CIs). We investigated statistical heterogeneity using I². RESULTS: Seven eligible studies (n = 433) were identified, which evaluated the effect on depression of CBT delivered individually (3 studies), in a group (3 studies) and by computer (1 study). The summary effect (SMD -0.61, 95% CI -0.96 to -0.26, p=0.0006) was reduced (SMD -0.46, 95% CI -0.75 to -0.17, p=0.002) when an outlying study was removed in a sensitivity analysis to examine statistical heterogeneity. Three studies (n=213) observed a direction of effect using the MSIS-29 which was not statistically significant (WMD -4.36, 95% CI -9.33 to 0.62, p=0.09). There was no between-subgroup heterogeneity (I²=0). CONCLUSIONS: CBT can be an effective treatment for depression in MS. Further research should explore optimal durations and modalities of treatment for patients with different characteristics.

Can temporal lobe epilepsy surgery ameliorate accelerated long-term forgetting?

Accelerated long-term forgetting (ALF) is a relatively newly identified phenomenon in neuropsychology which has been associated with temporal lobe epilepsy (TLE). ALF is characterised by intact acquisition and retention of memories over delays of minutes and hours, but abnormally fast forgetting over delays of 24h or more. The causes of ALF are unknown; however disruption of "slow" consolidation processes through seizure activity in the temporal lobes is proposed as a possible explanation. We looked to establish whether seizure control following epilepsy surgery ameliorated ALF in patients with TLE. Parallel sets of verbal and visual stimuli were administered comparing seven TLE patients and 25 healthy controls, matched on key demographic characteristics. Free recall and recognition were assessed at both pre-surgery/time 1 and post-surgery/time 2 at delays of 25 or 45 s, 30 min and one week. The TLE group retained significantly less verbally and visually learned material between 30 min and one week at the pre-surgery assessment than the control group. Comparison of the groups at post-surgery assessment indicated evidence of improved retention in the TLE group for both visual and verbal material, despite reduced initial registration on the verbal sub-tests. Exploratory analysis of individuals indicated heterogeneity in the patient group with regards to the presence/absence of ALF and post-surgical improvement in ALF. The findings offer some support to the theory that ALF is associated with uncontrolled seizures and that elimination of seizures via epilepsy surgery may improve retention by providing a stable environment for "slow" consolidation to occur. However, our results suggest that this is unlikely to be the sole cause and that "slow" consolidation may normally depend also on the integrity of structures within the neocortex or medial temporal lobes. Further investigation of these apparent heterogeneous groups may be informative in further defining the nature and causes of ALF.

Towards living well with young onset dementia: An exploration of coping from the perspective of those diagnosed.

There is increasing recognition that dementia in people under 65 years represents a unique challenge to sufferers and services alike. However, by either ignoring this population or sampling them together with older adults, current research has failed to reflect this. This study explored the specific experience of living and coping with Alzheimer's disease in younger life from the perspective of those diagnosed. Semi-structured interviews were analysed using interpretive phenomenological analysis, and four themes were identified: 'disruption of the life-cycle', 'identity', 'social orientation' and 'agency'. The experience of living and coping with young onset Alzheimer's disease was strongly situated within an individual's social context. Most significantly, participants felt too young to develop the disease and felt out of time with age-related psychological tasks. Coping strategies that attempted to redress and normalise the life-cycle were identified. The contributions of the study are discussed in the context of the human development literature.

Jazz, guitar, and neurosurgery: the Pat Martino case report.

OBJECTIVE: We present the case of a professional jazz guitarist with temporal lobe epilepsy secondary to an arteriovenous cerebral malformation. CASE DESCRIPTION: The patient underwent a left temporal lobectomy in 1980. After surgery, he presented with severe retrograde amnesia and complete loss of musical interest and capabilities. The patient's musical abilities recovered over time, and he regained his previous virtuoso status. In 2007, his medical history, neuropsychologic functions, and structural magnetic resonance imaging study were examined and revealed a remarkable degree of recovery of memory and musical abilities in the context of extensive temporal lobe resection. The neuropsychologic findings and neuroanatomic features of the magnetic resonance imaging study were analyzed to try to understand the high degree of recovery of both long-term memory and musical processing abilities in this musician. CONCLUSIONS: This case reveals the possibility of an unusual degree of cerebral plasticity and reorganization. Additionally, it emphasizes the question of musical virtuosity. This report shows that the musical capabilities of professional musicians, in specific cases, can completely recover even when much of the left temporal lobe has been removed.

Computerised cognitive behavioural therapy for the treatment of depression in people with multiple sclerosis: external pilot trial.

BACKGROUND: People with multiple sclerosis (MS) are at high risk of depression. We undertook a pilot trial of computerised cognitive behavioural therapy (CCBT) for the treatment of depression in people with MS to test the feasibility of undertaking a full trial. METHODS: Participants with a diagnosis of MS and clinical levels of depression were recruited through out-patient clinics and postal screening questionnaires at two UK centres and randomised to CCBT or usual care. Clinical outcomes included the Beck Depression Inventory (BDI-II) and Multiple Sclerosis Impact Scale (MSIS-29) at baseline, 8 and 21 weeks. Feasibility outcomes included: recruitment rate; reasons for refusal, withdrawal and dropout; feasibility and acceptability of the proposed outcome measures; sample size estimation and variation in and preferences for service delivery. RESULTS: Twenty-four participants were recruited. The recruitment rate, calculated as the proportion of those invited to fill in a screening questionnaire who were consented into the trial, was 4.1%. Recruitment through out-patient clinics was somewhat slower than through screening questionnaire mail-out but the overall recruitment yield was similar. Of the 12 patients in the CCBT arm, 9 (75%) completed at least four, and 6 completed all 8 CCBT sessions. For completers, the median time (IQR) to complete all eight CCBT sessions was 15 (13 to 20) weeks. Participants expressed concern about the face validity of the Beck Depression Inventory II for the measurement of self-reported depression in people with MS. The MSIS-29 was the patient-reported outcome measure which participants felt best reflected their concerns. The estimated sample size for a full trial is between 180 and 390 participants. NHS partners were not delivering CCBT in community facilities and participants preferred to access CCBT at home, with no one expressing a preference for use of CCBT in an alternative location. CONCLUSIONS: A definitive trial, with a recruitment window of one year, would require the participation of around 13 MS centres. This number of centres could be reduced by expanding the eligibility criteria to include either other neurological conditions or people with more severe depression. The MSIS-29 should be used as a patient-important outcome measurement. TRIAL REGISTRATION: ISRCTN: ISRCTN81846800.

Adversarial growth in patients with multiple sclerosis and their partners: relationships with illness perceptions, disability and distress.

The purpose of this study was to investigate whether patients with multiple sclerosis (MS) and their partners show adversarial growth and to examine which psychological and disability variables contribute to this in patients and their partners. The study also investigated the relationship between growth and distress. Seventy-two patients with MS and their partners provided demographic information and completed measures of posttraumatic growth, illness perceptions, depression, cognitive function and disability. Both patients and partners showed adversarial growth, with patients reporting significantly higher growth than partners. The only significant predictor for patient growth was partner growth, and vice versa. Dissimilarity in illness representations between patients and their partners on the consequences of MS dimension, patient mood and patient growth accounted for significant variance in partner growth. The findings support the idea of a 'communal search for meaning' where patients and their partners experience the trauma of having a chronic illness and subsequently find positive aspects together.

How do memory processes relate to the development of posttraumatic stress symptoms following childbirth?

Some women develop posttraumatic stress symptoms (PTSS) following childbirth but little is known about memory processes following childbirth. Models of traumatic memory debate the role of memory disorganization. This study investigates whether there is an association between memory disorganization and PTSS in new mothers. One hundred and twenty-two women were recruited within 72h of giving birth, completing measures of cognitive and emotional experience, and analgesia, and a narrative account of the birth. 68 of these women responded to a six-week follow-up and completed measures of memory disorganization and PTSS. There was a relationship between memory disorganization and PTSS at follow-up, but not at recruitment. The organization of the immediate narrative may not distinguish between those who later do or do not develop symptoms. Emotional evaluation may be the key factor in facilitating or inhibiting the memory construction process, linking memory to subsequent disorganization and hence to symptoms.

Depression in multiple sclerosis: reactive or endogenous?

Multiple sclerosis is associated with high rates of depression. The extent to which this is related to living with chronic illness or part of the disease process remains unclear. This question was investigated by comparing rates of depression in MS with those in rheumatoid arthritis, which involves similar physical and psychosocial stressors but without central nervous system involvement. The study involved an on-line survey, which included measures of depression not confounded by somatic symptoms, medication use, self-reported physical functioning, pain, and other demographic variables. Results indicated that disease group (multiple sclerosis, rheumatoid arthritis) independently predicted depression above and beyond demographic and disease-related variables. Results support the hypothesis that depression in MS is partly determined by direct neurological consequences of the condition.

A comparison of the development of audiovisual integration in children with autism spectrum disorders and typically developing children.

This study aimed to investigate the development of audiovisual integration in children with Autism Spectrum Disorder (ASD). Audiovisual integration was measured using the McGurk effect in children with ASD aged 7-16 years and typically developing children (control group) matched approximately for age, sex, nonverbal ability and verbal ability. Results showed that the children with ASD were delayed in visual accuracy and audiovisual integration compared to the control group. However, in the audiovisual integration measure, children with ASD appeared to 'catch-up' with their typically developing peers at the older age ranges. The suggestion that children with ASD show a deficit in audiovisual integration which diminishes with age has clinical implications for those assessing and treating these children.

The acceptability of computerised cognitive behavioural therapy for the treatment of depression in people with chronic physical disease: a qualitative study of people with multiple sclerosis.

BACKGROUND: People with chronic physical conditions are at elevated risk of depression. Due to a shortage of Cognitive Behavioural Therapy (CBT) practitioners, computerised CBT (CCBT) is recommended for people with mild to moderate depression. We assessed the applicability of CCBT for the treatment of depression in people with multiple sclerosis (MS). METHODS: Depth interviews with 17 people with MS and mild to moderate depression who used one of the two CCBT packages for either eight (Beating the Blues; n = 8) or five (MoodGym; n = 9) weekly sessions were analysed using 'Framework'. RESULTS: Participants found CCBT-use burdensome due to their physical symptoms. In addition to perpetuating social isolation, the lack of human input meant some participants were unable to define problems, set goals or distinguish between events, thoughts and beliefs as required. CCBT did not legitimise their grief over losses concomitant with their MS. They characterised depression symptom inventories as contaminated by somatic symptoms of their MS. One CCBT package (MoodGym) was perceived as using inappropriate case material for people with the symptoms of MS. CONCLUSIONS: It is likely that generic CCBT packages for the treatment of depression will need to be adapted for people with chronic physical conditions to maximise their potential for health benefit.

Memory complaints in epilepsy: an accurate reflection of memory impairment or an indicator of poor adjustment? A review of the literature.

People with epilepsy frequently complain of poor memory. Although organic memory impairment is one possible sequela of neuro-epilepsy variables, these complaints are not consistently supported by performance on objective measures. The current review has two objectives: first, to establish whether inconsistent results are an artifact of methodology and second, to collate existing published literature to identify possible explanations for inaccurate memory self-report in epilepsy. Review of the literature highlights many methodological limitations making it difficult to evaluate findings. However, it is apparent that in people with epilepsy, subjective memory demonstrates a greater relationship with anxiety and depression than with objective memory. We examine the hypothesis that memory complaints in epilepsy are a reflection of difficulties adjusting to, or coping with, the condition. Research has yet to identify any critical variables or pathways through which these factors influence perceptions of memory function. This review proposes a role for illness representations in understanding the nature of memory complaints in epilepsy.

What is it like to receive a diagnosis of nonepileptic seizures?

The aim of this qualitative study was to provide insight into the experience of receiving the diagnosis of nonepileptic seizures (NES) from the patient's perspective. Semistructured interviews were conducted with eight patients who had received the diagnosis of NES over the preceding 6 months. All participants were on a waiting list for psychological treatment. Verbatim records of the interviews were analyzed using interpretative phenomenological analysis (IPA). Six main themes emerged from the data ("the experience of living with nonepileptic seizures", "label and understanding", "being left in limbo land", "doubt and certainty", "feeling like a human being again", and "emotional impact of diagnosis"). An ability to integrate the diagnosis into a personal narrative was key to participants' acceptance of the diagnosis. The communication of the diagnosis left some participants feeling distressed. The results suggest that patients need more time and resources to understand the diagnosis and more support after they have received it.

A comparison of emotional and cognitive intelligence in people with and without temporal lobe epilepsy.

Medial temporal lobe structures have been hypothesized to be important in emotional intelligence (EI) and social cognition. There is some evidence associating temporal lobe epilepsy (TLE) with impairments in social cognition. This study aimed to establish whether TLE is also associated with deficits in EI. Sixteen patients with TLE and 14 controls without epilepsy matched for age and current intelligence quotient were compared on measures of EI, recognition of facial expressions of emotion, and distress. Results indicated that patients with TLE showed both impaired EI and impaired recognition of facial expressions. They also reported greater psychological distress, which correlated negatively with EI. It is suggested that some of the psychosocial problems experienced by patients with TLE can be conceptualized as the consequences of deficits in EI, possibly resulting from epilepsy-related disruption to medial temporal lobe functioning.