Reduced contrast sensitivity, pattern electroretinogram ratio, and diminished a-wave amplitude in patients with major depressive disorder.

The electroretinogram (ERG), a non-invasive electrophysiological tool used in ophthalmology, is increasingly applied to investigate neural correlates of depression. The present study aimed to reconsider previous findings in major depressive disorder (MDD) reporting (1) a diminished contrast sensitivity and (2) a reduced patten ERG (PERG) amplitude ratio, and additionally, to assess (3) the photopic negative response (PhNR) from the flash ERG (fERG), with the RETeval® device, a more practical option for clinical routine use. We examined 30 patients with a MDD and 42 healthy controls (HC), assessing individual contrast sensitivity thresholds with an optotype-based contrast test. Moreover, we compared the PERG ratio, an established method for early glaucoma detection, between both groups. The handheld ERG device was used to measure amplitudes and peak times of the fERG components including a-wave, b-wave and PhNR in both MDD patients and HCs. MDD patients exhibited diminished contrast sensitivity together with a reduced PERG ratio, compared to HC. With the handheld ERG device, we found reduced a-wave amplitudes in MDD, whereas no significant differences were observed in the fERG b-wave or PhNR between patients and controls. The reduced contrast sensitivity and PERG ratio in MDD patients supports the hypothesis that depression is associated with altered visual processing. The findings underscore the PERG's potential as a possible objective marker for depression. The reduced a-wave amplitude recorded with the RETeval® system in MDD patients might open new avenues for using handheld ERG devices as simplified approaches for advancing depression research compared to the PERG.

Interferometric carrier-envelope phase stabilization for ultrashort pulses in the mid-infrared.

We demonstrate an active carrier-envelope phase (CEP) stabilization scheme for optical waveforms generated by difference-frequency mixing of two spectrally detuned and phase-correlated pulses. By performing ellipsometry with spectrally overlapping parts of two co-propagating near-infrared generation pulse trains, we stabilize their relative timing to 18 as. Consequently, we can lock the CEP of the generated mid-infrared (MIR) pulses with a remaining phase jitter below 30 mrad. To validate this technique, we employ these MIR pulses for high-harmonic generation in a bulk semiconductor. Our compact, low-cost, and inherently drift-free concept could bring long-term CEP stability to the broad class of passively phase-locked OPA and OPCPA systems operating in a wide range of spectral windows, pulse energies, and repetition rates.

Autoantibody-associated psychiatric syndromes: a systematic literature review resulting in 145 cases.

BACKGROUND: Autoimmune encephalitis (AE) is an important consideration during the diagnostic work-up of secondary mental disorders. Indeed, isolated psychiatric syndromes have been described in case reports of patients with underlying AE. Therefore, the authors performed a systematic literature review of published cases with AE that have predominant psychiatric/neurocognitive manifestations. The aim of this paper is to present the clinical characteristics of these patients. METHODS: The authors conducted a systematic Medline search via Ovid, looking for case reports/series of AEs with antineuronal autoantibodies (Abs) against cell surface/intracellular antigens combined with predominant psychiatric/neurocognitive syndromes. The same was done for patients with Hashimoto encephalopathy/SREAT. Only patients with signs of immunological brain involvement or tumors in their diagnostic investigations or improvement under immunomodulatory drugs were included. RESULTS: We identified 145 patients with AE mimicking predominant psychiatric/neurocognitive syndromes. Of these cases, 64% were female, and the mean age among all patients was 43.9 (±22.1) years. Most of the patients had Abs against neuronal cell surface antigens (55%), most frequently against the NMDA-receptor (N = 46). Amnestic/dementia-like (39%) and schizophreniform (34%) syndromes were the most frequently reported. Cerebrospinal fluid changes were found in 78%, electroencephalography abnormalities in 61%, and magnetic resonance imaging pathologies in 51% of the patients. Immunomodulatory treatment was performed in 87% of the cases, and 94% of the patients responded to treatment. CONCLUSIONS: Our findings indicate that AEs can mimic predominant psychiatric and neurocognitive disorders, such as schizophreniform psychoses or neurodegenerative dementia, and that affected patients can be treated successfully with immunomodulatory drugs.

Reduced structural connectivity in the corpus callosum in patients with anorexia nervosa.

OBJECTIVE: Previous diffusion tensor imaging studies reported a reduced fractional anisotropy in the body of the corpus callosum in patients with anorexia nervosa, which may indicate impaired white matter integrity in interhemispheric connections. The aim of the current study was to investigate whether structural connectivity is affected in patients with anorexia nervosa. METHOD: To this end, we compared the number of streamlines (a model of the white matter fibre tracts) and the total volume filled by these streamlines in different subsections of the corpus callosum in 33 women with and 33 without anorexia nervosa as well as in 20 recovered individuals. RESULTS: The volume of streamlines in the anterior and mid-anterior subsection of the corpus callosum was reduced in women with, but not in those who had recovered from anorexia nervosa. No differences in number of streamlines was detected in the corpus callosum between patients with anorexia nervosa, healthy controls and recovered patients. CONCLUSIONS: Alterations of the corpus callosum have been repeatedly reported in anorexia nervosa. Since the recovered group did not differ from the healthy control group, the reported alterations in acute patients appear to represent a state and not a trait marker.

A case of co-occuring synesthesia, autism, prodigious talent and strong structural brain connectivity.

BACKGROUND: Synesthesia is a sensory phenomenon where certain domain-specific stimuli trigger additional sensations of e.g. color or texture. The condition occurs in about 4% of the general population, but is overrepresented in individuals with Autism Spectrum Disorder (ASD), where it might also be associated with the presence of prodigious talents. CASE PRESENTATION: Here we describe the case of a young transsexual man with Asperger Syndrome, synesthesia and a prodigious talent for foreign language acquisition. In our case, not only letters, numbers, spoken words, music, noises, weekdays and months lead to highly consistent, vivid color sensations but also his own and others' emotions, geometric shapes, any mathematical symbol, and letters from an unfamiliar alphabet (Hebrew). These color associations seem to aid categorization, differentiation and storage of information and might thereby contribute to the young man's language acquisition ability. We investigated the young man's structural brain connectivity in comparison to adults with or without ASD, applying global fiber tracking to diffusion-weighted Magnetic Resonance Imaging (MRI) data. The case presented with increased connectivity, especially between regions involved in visual and emotion processing, memory, and higher order associative binding regions. An electroencephalography experiment investigating synesthetic color and shape sensations while listening to music showed a negligible occipital alpha suppression, indicating that these internally generated synesthetic sensations derive from a different brain mechanism than when processing external visual information. CONCLUSIONS: Taken together, this case study endorses the notion of a link between synesthesia, prodigious talent and autism, adding to the currently still sparse literature in this field. It provides new insights into the possible manifestations of synesthesia in individuals with ASD and its potential contribution to prodigious talents in people with an otherwise unexceptional cognitive profile. Additionally, this case impressively illustrates how synesthesia can be a key element not only of sensory perception but also social and emotional processing and contributes to existing evidence of increased brain connectivity in association with synesthesia.

Increased IL-8 concentrations in the cerebrospinal fluid of patients with unipolar depression.

INTRODUCTION: Unipolar depression is a common and debilitating disorder. Immunological explanatory approaches have become increasingly important in recent years and can be studied particularly well in the cerebrospinal fluid (CSF). Previous studies discerned alterations in interleukin (IL)-6 and IL-8 levels; however, findings regarding IL-8 were partly contradictory. The aim of the present study was to investigate the concentrations of different cytokines and chemokines, focusing on IL-8, in the CSF of patients with unipolar depression. MATERIALS AND METHODS: Participants included 40 patients with unipolar depression and 39 mentally healthy controls with idiopathic intracranial hypertension. CSF cytokine levels were measured using a magnetic bead multiplexing immunoassay. RESULTS: IL-8 levels in the CSF of the patient group with depression were significantly higher than those in the control group (Mean ± SD: 38.44 ± 6.26 pg/ml versus 21.40 ± 7.96 pg/ml; p < .001). LIMITATIONS: The significance of the results is limited by the retrospective design and methodological aspects. DISCUSSION: The main findings of this study were significantly higher concentrations of IL-8 in the CSF of patients with unipolar depression than in the control group. The detection of high CSF IL-8 levels in this study supports the idea that inflammatory processes might play a role in the pathophysiology of a subgroup of patients with depression.

Altered cortical folding and reduced sulcal depth in adults with anorexia nervosa.

OBJECTIVE: Previous studies on anorexia nervosa (AN) focused on cortical volume and mainly reported grey matter reduction. They also investigated cortical surface parameters, for example, absolute mean curvature (AMC) providing information on cortical folding or sulcal depth (SD). For the first time, we also analysed cortical complexity using fractal dimension (FD) in AN. METHOD: In a cross-sectional study, we performed surface analyses (AMC, SD, and FD) on 34 women with AN, 24 recovered from AN (REC), and 41 healthy controls (HC). Structural MR data was processed using the Computational Anatomy Toolbox and statistically compared across groups on a vertex- and region-of-interest-wise level using statistical parametric mapping. RESULTS: We found a lower AMC and SD in AN, especially in temporal areas. FD was increased in the left precentral gyrus in AN. No differences of the parameters AMC, SD, or FD were evident between REC and HC participants. CONCLUSIONS: Alterations in AMC, SD, and FD in AN patients, but not between the REC and HC groups, suggest that these alterations are state related. The findings concur with other structural AN studies that suggest restitution with clinical recovery. The changes may be due to malnutrition, dehydration, osmotic dysregulation, or hormonal aberrations during the acute stage.

Neurobiological signature of intimacy in anorexia nervosa.

BACKGROUND: Intimacy and psychosexual development represent core problems of anorexia nervosa (AN). Experiential and neurobiological evidence however is scarce. MATERIAL AND METHODS: Thirty-one female AN patients were compared with 35 non-patients (NP) and 22 recovered participants (REC) by using functional magnetic resonance imaging. Participants viewed pictures of couples in intimate relationships and control stimuli. RESULTS: AN patients experienced intimate stimuli with lower valence and dominance. AN showed decreased activation of parietal cortices. NP decreased the prefrontal cortex response, which AN patients did not. REC participants did not differ from NP on a behavioural level, though with regard to the neural signature. DISCUSSION: Parietal cortices are related to processing of erotic themes, which seems to be deficient in AN. Dysfunction of prefrontal cortices likely mirrors dysfunctional control in AN. The neural signature does not seem to be state-related considering results of REC.

Recovery of cortical volume and thickness after remission from acute anorexia nervosa.

OBJECTIVE: Reduced grey (GM) and white matter (WM) volumes and increased cerebrospinal fluid (CSF) have been frequently reported in anorexia nervosa (AN), but studies focusing on cortical thickness (CT) are scarce and findings inconsistent. We conducted the first study in AN that analyzed both parameters in the same study to gain novel and comprehensive insight. METHOD: Voxel-based morphometry (VBM) analysis was performed on T1-weighted magnetic resonance images from 34 predominantly adult women with acute AN, 24 REC participants, and 41 healthy controls (HC). Global brain segment volumes (GM, WM, and CSF), regional GM volume, and cortical thickness measures were obtained from the same study sample. We further focused on recovery by including a REC group. RESULTS: The GM and WM volumes were decreased, and correspondingly, the CSF volume increased in the AN in comparison to the HC and REC groups. No significant volume differences between the REC and HC groups could be observed. AN patients showed reduced regional GM volumes in the right hippocampus and the left middle and right inferior frontal gyrus. Cortical thinning occurred in the AN group, which was particularly robust in fronto-parietal areas. The REC and HC groups failed to show any regional GM or cortical thickness differences. DISCUSSION: AN is accompanied by severe loss of brain volume and cortical thickness as assessed by complementary investigation tools. However, these changes seem to be largely reversible, which should be encouraging for therapists and patients. The underlying neurobiological mechanisms remain unclear and should be assessed in further studies.

Heterozygous deletion of SCN2A and SCN3A in a patient with autism spectrum disorder and Tourette syndrome: a case report.

BACKGROUND: Mutations in voltage-gated sodium channel (SCN) genes are supposed to be of importance in the etiology of psychiatric and neurological diseases, in particular in the etiology of seizures. Previous studies report a potential susceptibility region at the chromosomal locus 2q including SCN1A, SCN2A and SCN3A genes for autism spectrum disorder (ASD). To date, there is no previous description of a patient with comorbid ASD and Tourette syndrome showing a deletion containing SCN2A and SCN3A. CASE PRESENTATION: We present the unique complex case of a 28-year-old male patient suffering from developmental retardation and exhibiting a range of behavioral traits since birth. He received the diagnoses of ASD (in early childhood) and of Tourette syndrome (in adulthood) according to ICD-10 and DSM-5 criteria. Investigations of underlying genetic factors yielded a heterozygous microdeletion of approximately 719 kb at 2q24.3 leading to a deletion encompassing the five genes SCN2A (exon 1 to intron 14-15), SCN3A, GRB14 (exon 1 to intron 2-3), COBLL1 and SCL38A11. CONCLUSIONS: We discuss the association of SCN2A, SCN3A, GRB14, COBLL1 and SCL38A11 deletions with ASD and Tourette syndrome and possible implications for treatment.

Intrathecal Thyroid Autoantibody Synthesis in a Subgroup of Patients With Schizophreniform Syndromes.

Schizophreniform syndromes in combination with autoimmune thyroiditis and increased serum thyroid antibodies lead healthcare practitioners to consider a diagnosis of Hashimoto's encephalopathy. To detect specific biomarkers, the authors analyzed whether intrathecal antithyroid antibody synthesis occurred in a subgroup of schizophreniform patients. In doing so, the authors analyzed thyroid antibodies in paired cerebrospinal fluid and serum samples from 100 schizophreniform patients. Increased antibody indices (AIs) for antithyroid peroxidase or antithyroglobulin autoantibodies in 13 schizophreniform patients were found. AIs were increased in 68% of the seropositive patients. These findings support the hypothesis that autoimmune processes may contribute to the pathophysiology in these patients.

Increased rates of intermittent rhythmic delta and theta activity in the electroencephalographies of adult patients with attention-deficit hyperactivity disorder.

INTRODUCTION: Adult attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. In subgroups of patients with a (para)epileptic pathomechanism, this might be due to intermittent rhythmic delta or theta activity (IRDA/IRTA). PARTICIPANTS AND METHODS: Using a fully data-driven analysis, we compared the IRDA/IRTA rates in the resting electroencephalography (EEG) results of 97 adult patients with ADHD and 30 control subjects. The IRDA/IRTA rates before hyperventilation (HV) and for HV difference (difference between IRDA/IRTA rate after and before HV) were compared between groups using a linear model. RESULTS: We detected significantly increased rates of IRDA/IRTA before HV (F=4.209, p=0.042) in patients with ADHD but no significant difference between the groups for HV-difference (F=2.46, p=0.119). DISCUSSION: The increased IRDA/IRTA rates before HV in the group with ADHD might lead to (para)epileptic short-term effects (e.g., impulsivity) via local area network inhibition, and to long-term effects (e.g., cognitive deficits) via connectivistic brain restructuring.

Deficient amygdala-prefrontal intrinsic connectivity after effortful emotion regulation in borderline personality disorder.

Emotion instability in borderline personality disorder (BPD) has been associated with an impaired fronto-limbic inhibitory network. However, functional connectivity (FC) underlying altered emotion regulation in BPD has yet to be established. Here, we used resting-state fMRI to investigate enduring effects of effortful emotion regulation on the amygdala intrinsic FC in BPD. In this multicenter study, resting-state fMRI was acquired before and after an emotion regulation task in 48 BPD patients and 39 non-patient comparison individuals. The bilateral amygdalae were used as a seed in the whole-brain FC analysis and two-way mixed ANOVA to test whether BPD patients exhibited weaker post-task increase in the amygdala intrinsic FC with the prefrontal cortex (PFC), compared to non-patients. Subsequently, we explored whether the results are common for personality disorders characterized by emotional problems, using additional data of 21 cluster-C personality disorder patients. In contrast to non-patients, BPD patients failed to show increased post-task amygdala resting-state FC with the medial, dorsolateral, ventrolateral PFC, and superior temporal gyrus, but surprisingly exhibited decreased FC with the posterior cingulate cortex and increased FC with the superior parietal lobule. In BPD patients, the emotion regulation task failed to increase resting-state amygdala FC with brain regions essential for effortful emotion regulation, which suggests: (a) altered cognitive control typically used to indirectly alleviate distress by reinterpreting the meaning of emotional stimuli; (b) impaired direct regulation of emotional responses, which might be common for personality disorders;

615 fs pulses with 17 mJ energy generated by an Yb:thin-disk amplifier at 3 kHz repetition rate.

A combination of Er/Yb:fiber and Yb:thin-disk technology produces 615 fs pulses at 1030 nm with an average output power of 72 W. The regenerative amplifier allows variation of the repetition rate between 3 and 5 kHz with pulse energies from 13 to 17 mJ. A broadband and intense seed provided by the compact and versatile fiber front-end minimizes gain narrowing. The resulting sub-ps performance is ideal for nonlinear frequency conversion and pulse compression. Operating in the upper branch of a bifurcated pulse train, the system exhibits exceptional noise performance and stability.

The effect of methylphenidate intake on brain structure in adults with ADHD in a placebo-controlled randomized trial.

BACKGROUND: Based on animal research several authors have warned that the application of methylphenidate, the first-line drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease. METHODS: We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra. RESULTS: We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase. LIMITATIONS: Detecting possible neurotoxic effects of methylphenidate might require a longer observation period. CONCLUSION: There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.

Uncertain relational reasoning in the parietal cortex.

The psychology of reasoning is currently transitioning from the study of deductive inferences under certainty to inferences that have degrees of uncertainty in both their premises and conclusions; however, only a few studies have explored the cortical basis of uncertain reasoning. Using transcranial magnetic stimulation (TMS), we show that areas in the right superior parietal lobe (rSPL) are necessary for solving spatial relational reasoning problems under conditions of uncertainty. Twenty-four participants had to decide whether a single presented order of objects agreed with a given set of indeterminate premises that could be interpreted in more than one way. During the presentation of the order, 10-Hz TMS was applied over the rSPL or a sham control site. Right SPL TMS during the inference phase disrupted performance in uncertain relational reasoning. Moreover, we found differences in the error rates between preferred mental models, alternative models, and inconsistent models. Our results suggest that different mechanisms are involved when people reason spatially and evaluate different kinds of uncertain conclusions.

Hypoglutamatergic state is associated with reduced cerebral glucose metabolism in anti-NMDA receptor encephalitis: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was first described in 2005 in association with ovarian teratoma. The diagnostic workup of this common autoimmune encephalitis includes cerebrospinal fluid analysis, electroencephalography, magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (FDG-PET). In addition to standard diagnostics, we performed metabolic investigations using proton magnet resonance spectroscopy ((1)H-MRS). CASE PRESENTATION: We describe the case of a non-limbic anti-NMDAR encephalitis with a long course of disease (21 months). Laboratory diagnostics showed antibodies against NMDAR; an MRI revealed unspecific findings. (1)H-MRS indicated a hypoglutamatergic state in the left prefrontal cortex associated with a left hemispherical hypometabolism on FDG-PET. Despite the long course of disease, immunosuppressive therapy with methylprednisolone and azathioprine led to almost complete remission of clinical symptoms. Clinical improvement developed in parallel with remarkable normalization of cerebral glucose metabolism on FDG-PET. CONCLUSION: This case of long-lasting extra-limbic anti-NMDAR encephalitis is of high clinical relevance. First, it illustrates that a very good outcome is possible even if adequate therapy is started only 21 months after the onset of severe symptoms. Second, it provides valuable insights into the pathophysiology of such anti-NMDAR encephalitis; these insights prove that anti-NMDAR encephalitis is linked not only to hyperglutamatergic signals but also to hypoglutamatergic states. These findings, contradictory at first glance, can be integrated within the model of excitatory/inhibitory imbalance and local area network inhibition.

Fiber density estimation from single q-shell diffusion imaging by tensor divergence.

Diffusion-weighted magnetic resonance imaging provides information about the nerve fiber bundle geometry of the human brain. While the inference of the underlying fiber bundle orientation only requires single q-shell measurements, the absolute determination of their volume fractions is much more challenging with respect to measurement techniques and analysis. Unfortunately, the usually employed multi-compartment models cannot be applied to single q-shell measurements, because the compartment's diffusivities cannot be resolved. This work proposes an equation for fiber orientation densities that can infer the absolute fraction up to a global factor. This equation, which is inspired by the classical mass preservation law in fluid dynamics, expresses the fiber conservation associated with the assumption that fibers do not terminate in white matter. Simulations on synthetic phantoms show that the approach is able to derive the densities correctly for various configurations. Experiments with a pseudo ground truth phantom show that even for complex, brain-like geometries the method is able to infer the densities correctly. In-vivo results with 81 healthy volunteers are plausible and consistent. A group analysis with respect to age and gender show significant differences, such that the proposed maps can be used as a quantitative measure for group and longitudinal analysis.

Emotional modulation of motor response inhibition in women with borderline personality disorder: an fMRI study.

BACKGROUND: Both emotion regulation and impulsivity are core aspects of borderline personality disorder (BPD) pathology. Although both problems may be combined specifically in BPD, few studies to date have investigated the emotional modulation of impulsivity in BPD. METHODS: Women with BPD and matched healthy controls performed go/no-go tasks after induction of anger, joy or a neutral mood by vocally presented short stories. Dependent variables were the behavioural results and functional magnetic resonance imaging data. RESULTS: We included 17 women with BPD and 18 controls in our study. No behavioural group differences were found. However, patients with BPD showed stronger activation of the left amygdala and weaker activation of the subgenual anterior cingulate during anger induction than controls. Inhibition in the go/no-go task after anger induction increased activity in the left inferior frontal cortex in controls, but not in women with BPD, who, in turn, showed increased activation in the subthalamic nucleus. LIMITATIONS: Findings cannot be generalized to men, and 4 patients were taking antidepressant medication (selective serotonin reuptake inhibitors). In addition, no patient control group was investigated, thus we do not know whether findings are specific to BPD compared with other disorders. CONCLUSION: Our findings are consistent with the view that a disturbed amygdala-prefrontal network in patients with BPD is compensated by a subcortical loop involving the subthalamic nucleus, leading to normal behavioural inhibition in these patients.