Social and psychological consequences of not crying: possible associations with psychopathology and therapeutic relevance.

OBJECTIVE: Emotional crying is hypothesized to serve intra- and interpersonal functions. Intrapersonal functions are assumed to facilitate the capacity to recover from emotional distress, thus promoting well-being. Interpersonal functions are postulated to have a major impact on social functioning. We hypothesized that non-criers would have lower well-being and poorer social functioning than criers. METHODS: Study participants included 475 people who reportedly lost the capacity to cry and 179 "normal" control criers. Applied measures assessed crying, well-being, empathy, attachment, social support, and connection with others. Prevalence estimates of not crying by gender were obtained from a panel survey of 2,000 Dutch households. RESULTS: In the main survey, tearless cases had less connection with others, less empathy, and experienced less social support, but were equal in terms of well-being. They also reported being less moved by emotional stimuli and had a more avoidant and less anxious attachment style. In multivariate analyses, being male, having an avoidant attachment style, and lacking empathy were independent predictors of tearlessness. Some 46.1% felt that not being able to cry affected them negatively; however, despite these findings, only 2.9% had sought any kind of professional help. Loss of the capacity to cry occurred in 8.6% of the men and 6.5% of the women in the large panel survey. CONCLUSIONS: Despite reduced empathy, less connection with others, and a more avoidant/less anxious attachment type, well-being is maintained in tearless people. Additional clinical and therapeutic investigations of tearlessness may lead to clarification of bidirectional associations between psychiatric disorders (e.g., alexithymia, posttraumatic stress disorder, psychopathy) and tearlessness.

Neuropsychiatry of creativity.

In this paper, we review in brief the development of ideas that over time have tried to explain why some individuals are more creative than others and what may be the neurobiological links underlying artistic creativity. We note associations with another unique human idea, that of genius. In particular, we discuss frontotemporal dementia and bipolar, cyclothymic mood disorder as clinical conditions that are helping to unravel the underlying neuroanatomy and neurochemistry of human creativity. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity".

Long-term effects of electrodermal biofeedback training on seizure control in patients with drug-resistant epilepsy: two case reports.

We report data from two patients, followed over 3 years after electrodermal biofeedback treatment. Patients were trained three times each week for four weeks to increase their sympathetic arousal using electrodermal biofeedback. This treatment was directed at enabling the patients to change their psychophysiological state as a countermeasure to prevent seizures. Both patients voluntarily kept a record of seizure frequency over the year preceding the treatment and continued to record their seizures for up to 3 years after the termination of biofeedback treatment. Both patients showed a marked reduction in seizure frequency (54.9% and 59.8%) during the month of biofeedback treatment. This improvement was maintained over the subsequent years. We highlight the therapeutic potential of biofeedback interventions that enable patients to volitionally control their state of physiological arousal in the management of drug-resistant epilepsy.

Cerebellar volume is linked to cognitive function in temporal lobe epilepsy: a quantitative MRI study.

INTRODUCTION: Chronic intractable temporal lobe epilepsy (TLE) is associated with certain comorbidities including cognitive impairment. A less common condition among patients with TLE is intermittent explosive disorder (IED), a specific form of aggressive behavior that has been linked to low intelligence and structural pathology in the amygdala. We aimed to identify other neuroanatomical substrates of both cognitive dysfunction and IED in patients with TLE, with special focus on the cerebellum, a brain region known to participate in functional networks involved in neuropsychological and affective processes. METHODS: Magnetic resonance imaging-based volumetric data from 60 patients with temporal lobe epilepsy (36 with and 24 without IED) were evaluated. Cerebellar, hippocampal, and total brain volumes were processed separately. In a total of 50 patients, the relationship between volumetric measurements and clinical and neuropsychological data (full-scale, verbal, and performance intelligence quotients) was analyzed. RESULTS: Intermittent explosive disorder in patients with TLE was not significantly linked to any of the regional volumes analyzed. However, cognitive performance showed a significant association both with total brain volume and cerebellar volume measurements, whereby the left cerebellar volume showed the strongest association. A deviation from normal cerebellar volumes was related to lower intelligence. Of note, left cerebellar volume was influenced by age and duration of epilepsy. Hippocampal volumes had a minor influence on cognitive parameters. CONCLUSION: Our findings suggest that cerebellar volume is not linked to IED in patients with TLE but is significantly associated with cognitive dysfunction. Our findings support recent hypotheses proposing that the cerebellum has a relevant functional topography.

The functional neuroimaging correlates of psychogenic versus organic dystonia.

The neurobiological basis of psychogenic movement disorders remains poorly understood and the management of these conditions difficult. Functional neuroimaging studies have provided some insight into the pathophysiology of disorders implicating particularly the prefrontal cortex, but there are no studies on psychogenic dystonia, and comparisons with findings in organic counterparts are rare. To understand the pathophysiology of these disorders better, we compared the similarities and differences in functional neuroimaging of patients with psychogenic dystonia and genetically determined dystonia, and tested hypotheses on the role of the prefrontal cortex in functional neurological disorders. Patients with psychogenic (n = 6) or organic (n = 5, DYT1 gene mutation positive) dystonia of the right leg, and matched healthy control subjects (n = 6) underwent positron emission tomography of regional cerebral blood flow. Participants were studied during rest, during fixed posturing of the right leg and during paced ankle movements. Continuous surface electromyography and footplate manometry monitored task performance. Averaging regional cerebral blood flow across all tasks, the organic dystonia group showed abnormal increases in the primary motor cortex and thalamus compared with controls, with decreases in the cerebellum. In contrast, the psychogenic dystonia group showed the opposite pattern, with abnormally increased blood flow in the cerebellum and basal ganglia, with decreases in the primary motor cortex. Comparing organic dystonia with psychogenic dystonia revealed significantly greater regional blood flow in the primary motor cortex, whereas psychogenic dystonia was associated with significantly greater blood flow in the cerebellum and basal ganglia (all P < 0.05, family-wise whole-brain corrected). Group × task interactions were also examined. During movement, compared with rest, there was abnormal activation in the right dorsolateral prefrontal cortex that was common to both organic and psychogenic dystonia groups (compared with control subjects, P < 0.05, family-wise small-volume correction). These data show a cortical-subcortical differentiation between organic and psychogenic dystonia in terms of regional blood flow, both at rest and during active motor tasks. The pathological prefrontal cortical activation was confirmed in, but was not specific to, psychogenic dystonia. This suggests that psychogenic and organic dystonia have different cortical and subcortical pathophysiology, while a derangement in mechanisms of motor attention may be a feature of both conditions.

"All that spikes is not fits", mistaking the woods for the trees: the interictal spikes--an "EEG chameleon" in the interface disorders of brain and mind: a critical review.

Recent research into mammalian cortical neurophysiology, after 6 decades of Berger's seminal work on electroencephalography, has shifted the older concept of interictal epileptiform activity (IEA) away from that of a mere electrographic graphoelement of relevance to diagnostic implications in epilepsy. Instead, accumulating information has stressed the neuropsychological implications, cognitive and/or behavioral consequence of these electrophysiological events, which are the phenotypic expression of aberrations of actual biophysical cellular function. We feel that this review is germane to neuropsychiatry, however, a rather neglected area of research. There is a great scope for brain-behavior-EEG research in the future that can be complimented by other techniques of "neurobehavioral electrophysiology". This review does not address the "pearls, perils and pitfalls" in the use of EEG in epilepsy, but critically and systematically reappraises the published electroencephalographic correlates of human behavior. We reiterate that epileptiform and other paroxysmal EEG dysrhythmias unrelated to clinical seizures do have neuropsychological, cognitive and/or behavioral implications as seen in the various neuropsychiatric and neurobehavioral disorders discussed in this article. IEA and EEG dysrhythmias should neither be ignored as irrelevant nor automatically attributed to epilepsy. The relevance of these EEG aberrations in the disorders of the brain-mind interface extend beyond epilepsy, and may be an electrophysiological endophenotype of aberrant neuronal behavior indicative of underlying morpho-functional brain abnormalities. Magnetoencephalography (MEG), data fusion models (EEG-fMRI-BOLD), transcranial magnetic stimulation (TMS), evoked potentials (EP); intracranial electrophysiology, and EEG neurofeedback complemented by current functional neuroimaging techniques (fMRI and PET) would certainly help in further understanding the broader relationship between brain and behavior.

Epilepsy, psychiatry, and neurology.

This article reviews the relationship between the psychiatry and neurology of epilepsy, especially in the last 100 years. Throughout most of its recorded history of 3 to 4 millennia epilepsy has been viewed as a supernatural or mental disorder. Although first suggested by Hippocrates in the 5th century B.C., the concept of epilepsy as a brain disorder only began to take root in the 17th and 18th centuries. The discipline of neurology emerged from "nervous disorders" or neuropsychiatry in the late 19th century, when vascular theories of epilepsy predominated. By the turn of the 19th century psychiatry and neurology were diverging and epilepsy remained to some extent in both disciplines. It was only in the middle of the 20th century with the development of electromagnetic theories of epilepsy that the concept of epilepsy per se as a neurological disorder was finally adopted in international classifications of disease. This was associated with a refined definition of the ictal, pre-, post-, and interictal psychological disorders of epilepsy, which have contributed to a renaissance of neuropsychiatry. At the beginning of the 21st century and the centenary of the ILAE psychiatry and neurology have been converging again, led in some respects by epilepsy, which has provided several useful models of mental illness and a bridge between the two disciplines.

Music and madness: neuropsychiatric aspects of music.

Music has soothed the souls of human beings for centuries and it has helped people recover from ailments since ancient times. Today, there is still a widespread interest in the relationship between music, affect and mental illness. This article is aimed at reviewing these complex relationships, starting from a wide perspective on the neurobiology of emotions, perceptions and music language to a detailed analysis of psychopathology in famous musicians.

Antiepileptic drug-induced cognitive adverse effects: potential mechanisms and contributing factors.

Cognitive dysfunction is frequently observed in patients with epilepsy and represents an important challenge in the management of patients with this disorder. In this respect, the relative contribution of antiepileptic drugs (AEDs) is of relevance. The fact that a considerable number of patients require AED therapy for many years, or perhaps even a lifetime, emphasizes the need to focus on the long-term adverse effects of these drugs on cognition. The most prevalent of the CNS adverse effects observed during AED therapy are sedation, somnolence, distractibility, insomnia and dizziness. Sedation, in particular, is associated with most of the commonly used AED therapies. Nevertheless, cognitive function in individuals with epilepsy may also be influenced by several factors, of which AEDs constitute only one of many putative causes. In general terms, most studies agree that some differences exist among the older AEDs with regard to the effects on cognition, and some newer generation molecules may have a better cognitive profile than older AEDs. The mechanisms of action are an obvious determinant; however, there is still a lack of evidence for differentiation between available drugs with regard to cognitive effects. Some authors have suggested that there may be different cognitive effects associated with individual drugs; however, the question as to whether there are more specific deficits related to the action of individual drugs remains unsolved. There seems to be agreement that polytherapy and high-dose treatment can produce cognitive adverse effects and when high dosages or adjunctive polytherapy is needed, the balance between benefits and disadvantages may be negatively biased against drug treatment. Thus, drug treatment requires careful balancing in the attempt to reach maximal seizure control while avoiding neurotoxic adverse effects. Finally, the mood status of the patient and clinical relevance of the information obtained by neuropsychological testing represent important variables that need to be taken into account when discussing cognitive adverse effects of AEDs.

Changes in cortical potential associated with modulation of peripheral sympathetic activity in patients with epilepsy.

OBJECTIVES: To examine the immediate and sustained effects of volitional sympathetic modulation, using galvanic skin response (GSR) biofeedback training on cortical excitability in patients with drug-resistant epilepsy. METHODS: Ten patients undertook 12 sessions of GSR biofeedback training over 1 month, during which they were trained to increase sympathetic arousal, using GSR biofeedback. Contingent negative variation (CNV) (a slow cortical potential reflecting cortical arousal and excitability) and the related post imperative negative variation (PINV) were quantified before and after biofeedback treatment. RESULTS: A significant reduction in CNV amplitude was observed in both the short-term (within the first session, after 10 minutes of GSR biofeedback) and long-term (sustained after 12 training sessions). Specifically, the change in baseline CNV amplitude after the 12 training sessions correlated with a percentage reduction in seizure frequency. Furthermore, changes in baseline amplitude of the PINV also correlated with seizure reduction. CONCLUSIONS: Our findings demonstrate that behavioral enhancement of peripheral sympathetic tone (GSR) is associated with modulation of indices of cortical excitability. Moreover, GSR biofeedback training over repeated sessions was associated with a chronic baseline reduction in slow cortical potentials and concurrent therapeutic improvement.

On the prevalence of bipolar disorder in epilepsy.

Although mood disorders represent a frequent psychiatric comorbidity in epilepsy, data on bipolar disorder (BD) are still limited, and the role of possible specific confounding variables (seizures and antiepileptic drug therapy) has never been considered. Data for 143 adult outpatients with epilepsy assessed with the Mini International Neuropsychiatric Interview Plus Version 5.0.0 using the Epilepsy Addendum for Psychiatric Assessment, the Mood Disorder Questionnaire, and the Interictal Dysphoric Disorder Inventory revealed that 11.8% had the Diagnostic and Statistical Manual of Mental Disorders-based diagnosis of BD, only 1.4% of whom could be considered as having "pure" BD, because in all other cases BD symptoms were related to phenotype copies of BD such as interictal dysphoric disorder of epilepsy, postictal manic or hypomanic states, and preictal dysphoria.

Electroencephalographic cerebral dysrhythmic abnormalities in the trinity of nonepileptic general population, neuropsychiatric, and neurobehavioral disorders.

Subclinical electroencephalographic epileptiform discharges in neurobehavioral disorders are not uncommon. The clinical significance and behavioral, diagnostic, and therapeutic implications of this EEG cerebral dysrhythmia have not been fully examined. Currently the only connotation for distinctive epileptiform electroencephalographic patterns is epileptic seizures. Given the prevailing dogma of not treating EEGs, these potential aberrations are either disregarded as irrelevant or are misattributed to indicate epilepsy. This article reappraises the literature on paroxysmal EEG dysrhythmia in normative studies of the "healthy" nonepileptic general populations, neuropsychiatry, and in neurobehavioral disorders. These EEG aberrations may be reflective of underlying morpho-functional brain abnormalities that underpin various neurobehavioral disturbances.

Are psychiatric adverse events of antiepileptic drugs a unique entity? A study on topiramate and levetiracetam.

PURPOSE: To investigate the hypothesis that some patients with epilepsy are generally prone to develop psychiatric adverse events (PAEs) during antiepileptic drug (AED) therapy irrespective of the mechanism of action of the drugs. METHODS: From a large case registry of patients prescribed topiramate (TPM) and levetiracetam (LEV), data of patients who had a trial with both drugs were analyzed. Demographic and clinical variables of those who developed PAEs with both drugs (group 1) were compared with those who did not (group 2). Subsequently, from the whole case registry, psychopathological features, demographic, and clinical variables of patients developing PAEs with TPM were compared with those of patients developing PAEs with LEV. RESULTS: The case registry included over 800 patients. Among 108 patients having a trial with both drugs, we identified 9 patients in group 1 and 71 in group 2. Previous psychiatric history, family psychiatric history and history of febrile convulsions showed to be significant clinical correlates. Comparing patients who developed PAEs with LEV with those who developed PAEs with TPM, there were no differences in epilepsy related variables. Well-defined DSM-IV disorders were more frequent with TPM than with LEV. Seizure freedom was associated with psychosis. CONCLUSIONS: This study suggests that a subgroup of patients is generally prone to develop PAEs during AED therapy, despite different pharmacological properties of the AEDs. A particular clinical profile and relevant variables have been identified.

Vagus nerve stimulation for treatment-resistant depression: behavioral and neural effects on encoding negative material.

OBJECTIVES: Vagus nerve stimulation (VNS) can improve depression. Cognitive models of depression highlight an over-representation of negative thoughts and memories, with depressed individuals showing memory facilitation for negative material. We hypothesized that the antidepressant action of VNS may emerge through corrective influences on 'negativity bias' in memory. We therefore examined the impact of VNS on emotional memory and its underlying brain activity. METHODS: We tested a single patient undergoing VNS for treatment-resistant depression (TRD). Stimulation was set at a 30/66-second on/off cycle during three encoding blocks when the patient viewed randomly presented positive, negative, and neutral words. Following each block, VNS was switched off and the patient identified previously seen words from distractors in a subsequent recognition memory task. The patient was scanned using functional magnetic resonance imaging (fMRI) during the first encoding block. RESULTS: There was robust recall of negative material viewed during 'off' cycles of VNS but subsequent memory of negative words was attenuated during active VNS ('on' cycles). VNS did not influence memory for neutral and positive words. With neuroimaging, direct modulatory effects of VNS were observed in dorsomedial, dorsolateral, and orbital regions of the prefrontal cortex. Moreover, during encoding of negative words, compared with positive and neutral words, VNS also modulated activity within orbitofrontal, ventromedial and polar prefrontal cortices, midcingulate cortex, and brain stem. CONCLUSIONS: Our observations show that VNS can interfere with memory of negative information, an effect that may contribute to its antidepressant role. Neuroimaging implicated regions including the ventral and medial prefrontal cortex as an underlying neural substrate.

The role of hippocampal sclerosis in antiepileptic drug-related depression in patients with epilepsy: a study on levetiracetam.

OBJECTIVE: Hippocampal sclerosis (HS) has been described as a relevant factor for the development of topiramate-related depression and cognitive deficits. The aim of our study was to clarify whether patients with temporal lobe epilepsy (TLE) and HS were also at risk during therapy with levetiracetam (LEV). METHODS: Data of 156 patients was analysed: 78 with TLE and HS and 78 with TLE and normal MRI matched for age, starting dose and titration schedule of LEV. Patients were selected from a population of consecutive patients started on LEV between 2000 and 2002. RESULTS: No differences were observed in prevalence of cognitive adverse events and depression between the two groups. CONCLUSIONS: LEV treatment is not associated with cognitive adverse events and depression in patients with hippocampal sclerosis.

Neuropharmacological aspects of cognitive neurorehabilitation in epilepsy.

The role of CNS neuromodulators in cognitive neurorehabilitation can be related to two main issues: 1) the negative impact on cognition of drug categories prescribed for different neurologic symptoms, such as spasticity, extrapyramidal symptoms, or epileptic seizures; 2) their possible role in neuroprotection and amelioration of the cognitive status of the patient, especially attention and memory. This paper reviews different pharmacological aspects of cognitive neurorehabilitation in epilepsy.