Comparison of magnetic resonance angiography techniques to brain digital subtraction arteriography in the setting of mechanical thrombectomy: A non-inferiority study.

INTRODUCTION: We performed a non-inferiority study comparing magnetic resonance angiography (MRA) techniques including contrast-enhanced (CE) and time-of-flight (TOF) with brain digital subtraction arteriography (DSA) in localizing occlusion sites in acute ischemic stroke (AIS) with a prespecified inferiority margin taking into account thrombus migration. MATERIALS AND METHODS: HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) includes large-vessel-occlusion (LVO) AIS treated with mechanical thrombectomy (MT) following brain magnetic resonance imaging (MRI) including both CE-MRA and TOF-MRA. Locations of arterial occlusions were assessed independently for both MRA techniques and compared to brain DSA findings. Number of patients needed was 48 patients to exclude a difference of more than 20%. Discrepancy factors were assessed using univariate general linear models analysis. RESULTS: The study included 151 patients with a mean age of 67.6±15.9years. In all included patients, TOF-MRA and CE-MRA detected arterial occlusions, which were confirmed by brain DSA. For CE-MRA, 38 (25.17%) patients had discordant findings compared with brain DSA and 50 patients (33.11%) with TOF-MRA. The discordance factors were identical for both MRA techniques namely, tandem occlusions (OR=1.29, P=0.004 for CE-MRA and OR=1.61, P<0.001 for TOF-MRA), proximal internal carotid artery occlusions (OR=1.30, P=0.002 for CE-MRA and OR=1.47, P<0.001 for TOF-MRA) and time from MRI to MT (OR=1.01, P=0.01 for CE-MRA and OR=1.01, P=0.02 for TOF-MRA). CONCLUSION: Both MRA techniques are inferior to brain DSA in localizing arterial occlusions in LVO-AIS patients despite addressing the migratory nature of the thrombus.

Multifocal arterial wall contrast - enhancement in ischemic stroke: A mirror of systemic inflammatory response in acute stroke.

PURPOSE: Intracranial plaque gadolinium enhancement revealed by high-resolution MRI imaging (HR MRI) is considered as a marker of plaque inflammation, a contributing factor of plaque unstability. The aim of the present study was to assess the distribution of gadolinium enhancement in intracranial atherosclerosis. METHODS: Single center analysis of ischemic stroke patients with intracranial atherosclerotic stenosis of M1 or M2 segments of middle cerebral artery, or terminal internal carotid artery (ICA) based on CT-angio or MR-angio. High-resolution MRI imaging (HRMRI) was performed within 6 first weeks following the index event, with 3DT2 BB (black-blood) and 3D T1 BB MR sequences pre and post-contrast administration. RESULTS: We identified 8 patients with 14 plaques, 4 were deemed non-culprit and 10 culprit. All culprit plaques (10/10 plaques) and 3 out of 4 non-culprit plaques showed a gadolinium enhancement. CONCLUSION: At the acute/subacute stage of stroke, a gadolinium enhancement may affect multiple asymptomatic intracranial plaques and may reflect a global inflammatory state.

Early Detection of Underlying Cavernomas in Patients with Spontaneous Acute Intracerebral Hematomas.

BACKGROUND AND PURPOSE: Early identification of the etiology of spontaneous acute intracerebral hemorrhage is essential for appropriate management. This study aimed to develop an imaging model to identify cavernoma-related hematomas. MATERIALS AND METHODS: Patients 1-55 years of age with acute (≤7 days) spontaneous intracerebral hemorrhage were included. Two neuroradiologists reviewed CT and MR imaging data and assessed the characteristics of hematomas, including their shape (spherical/ovoid or not), their regular or irregular margins, and associated abnormalities including extralesional hemorrhage and peripheral rim enhancement. Imaging findings were correlated with etiology. The study population was randomly split to provide a training sample (50%) and a validation sample (50%). From the training sample, univariate and multivariate logistic regression was performed to identify factors predictive of cavernomas, and a decision tree was built. Its performance was assessed using the validation sample. RESULTS: Four hundred seventy-eight patients were included, of whom 85 had hemorrhagic cavernomas. In multivariate analysis, cavernoma-related hematomas were associated with spherical/ovoid shape (P < .001), regular margins (P = .009), absence of extralesional hemorrhage (P = .01), and absence of peripheral rim enhancement (P = .002). These criteria were included in the decision tree model. The validation sample (n = 239) had the following performance: diagnostic accuracy of 96.1% (95% CI, 92.2%-98.4%), sensitivity of 97.95% (95% CI, 95.8%-98.9%), specificity of 89.5% (95% CI, 75.2%-97.0%), positive predictive value of 97.7% (95% CI, 94.3%-99.1%), and negative predictive value of 94.4% (95% CI, 81.0%-98.5%). CONCLUSIONS: An imaging model including ovoid/spherical shape, regular margins, absence of extralesional hemorrhage, and absence of peripheral rim enhancement accurately identifies cavernoma-related acute spontaneous cerebral hematomas in young patients.

Increased distractibility in schizophrenic patients. Electrophysiologic and behavioral evidence.

The inability of schizophrenics to filter irrelevant information has often been implicated in the psychopathology of schizophrenia. Despite numerous attempts at characterizing the behavior of schizophrenics in the presence of distractors, evidence of increased distractibility has been equivocal due to the difficulty of assessing simultaneously the behavioral and neurophysiological effects of distracting stimuli. We report the results of an experiment in which event-related potential and performance measures were used to assess distractibility during reaction time tasks under different distracting conditions. The results supported the view of an increased distractibility in schizophrenic patients. Event-related potential data suggested that in schizophrenic patients, a reduced amount of processing resources is allocated to process external stimuli and attention is abnormally apportioned to task-irrelevant vs task-relevant stimuli.

N400 and semantic categorization in schizophrenia.

The N400 component of event-related potentials (ERPs) was investigated in medicated schizophrenic patients and normal controls in a semantic categorization task. The subjects' task was to indicate whether pairs of words were semantically related or unrelated. The ERPs to the unrelated second words of the pairs contained a negative component, N400, which was reduced and delayed in the patients. However, inspection of individual subjects' data indicated that N400 was abnormal only in a subgroup of schizophrenics. Abnormalities in the amplitude of N400 suggest impairments in semantic expectancies, whereas abnormalities in the latency of N400 suggest a delay in information processing.

Fear-potentiated startle: relationship to the level of state/trait anxiety in healthy subjects.

The startle reflex is potentiated during experimentally induced anxiety (fear-potentiated startle). It is also increased in various anxiety disorders. The present study investigated the relationship between individual differences in fear and anxiety, and startle modulation. The eyeblink component of the acoustic startle reflex was measured in a paradigm involving the anticipation of electric shocks in 22 healthy men who were volunteers. Each subject's fear of shock was assessed with the state portion of the State-Trait Anxiety Inventory (STAI; Spielberger 1983). Fear-potentiated startle, but not baseline startle, differed in the low and high fear subjects. The magnitude of fear-potentiated startle was larger in the high-fear group as compared to the low-fear group. The time-course of startle modulation suggested a longer duration of anticipatory anxiety in the high-fear group. Trait anxiety, which was assessed with the trait portion of the STAI, did not relate to individual differences in either baseline or fear-potentiated startle.

Startle gating deficits occur across prepulse intensities in schizophrenic patients.

The effects of prepulse stimuli of different intensities in inhibiting the startle reflex was assessed in 14 age-matched and gender-matched schizophrenic patients and 14 normal controls. The subjects were presented with startling stimuli consisting of bursts of white noise (106 dBA) with or without prepulse stimuli. Four intensities of prepulse stimuli were utilized: 75, 80, 85, and 90 dBA. Throughout the testing, the background noise was maintained at 70 dBA. The prepulse stimuli more effectively inhibited the startle reflex in the control group compared to the schizophrenic patients who showed deficient prepulse inhibition (gating) of the startle reflex. These results suggest that schizophrenics have impaired central inhibitory mechanisms over a fairly broad range of background noise to prepulse ratios. Further studies are needed to clarify exactly which ratios are optimal in eliciting prepulse inhibition (PPI) and in differentiating between schizophrenic and control groups.

Baseline and fear-potentiated startle in panic disorder patients.

The present study investigated whether patients with panic disorder had an increase in the startle response and whether this effect, if present, was specific to anticipatory anxiety. The eyeblink component of the acoustic startle reflex was measured in a paradigm involving the anticipation of electric shocks (fear-potentiated startle) in 34 patients with panic disorder and 49 healthy controls. Startle was also recorded in the absence of specific threat at the beginning and at the end of the testing. The testing consisted of three phases: adaptation, fear-potentiated startle, and recovery. In the adaptation and recovery phases, startle stimuli were delivered in the absence of threat. In the fear-potentiated startle phase, startle stimuli were delivered in threat conditions, when subjects anticipated shocks, and in safe conditions that predicted the absence of shocks. Startle was larger in the younger patients (age < 40 years old) compared to the younger controls throughout the testing. The difference reached significance only during the fear-potentiated startle phase, however. Startle was nonsignificantly reduced in the older patients (age > or = 39 years old), compared to the older controls. The results are discussed in terms of the contextual effects of the experimental setting.

Middle latency auditory evoked potentials (MAEPs) in chronic schizophrenics.

Middle latency auditory evoked potentials were recorded in medicated chronic schizophrenics and controls at stimulation rates of 10/s, 2/s, and 1/s. Increasing the stimulation rate did not change Pa amplitude but decreased Pb amplitude. There was no difference between the two groups.

Effects of task relevance and attention on P3 in schizophrenic patients.

The P3 component of the event-related potentials (ERPs) to auditory task-relevant and task-irrelevant stimuli in 'Attend Auditory' (i.e., reaction time task) and 'Attend Visual' (i.e., when the auditory stimuli were being ignored) conditions was investigated in 13 RDC/DSM-III diagnosed schizophrenic patients. ERPs were recorded from Fz, Cz, and Pz. Compared to controls, schizophrenics had a significantly smaller P3 in the Attend Auditory than in the Attend Visual condition and to the task-relevant than to the task-irrelevant stimuli. Furthermore, the patients' P3 response to the most salient task-irrelevant stimuli in the Attend visual condition was normal. The results are discussed as suggesting that schizophrenics either allocate relatively more resources to task-irrelevant than task-relevant stimuli or that they fail to habituate to task-irrelevant stimuli.

Visual memory processes in high-functioning individuals with autism.

High-functioning autistic individuals were compared with age-matched normal control subjects on a visual recognition memory task. In order to evaluate the effects of "meaning" and "delay" on the visual memory of autistic individuals, meaningful (pictures) and meaningless (nonsense shapes) stimuli were presented visually in no delay and 1-minute delay intervals to both groups. It was concluded that autistic subjects perform particularly poorly on meaningless material, but they are able to utilize meaning to aid their visual memory. Contrary to expectations, 1-minute delay intervals did not differentially affect the visual memory performance of autistic individuals compared to control subjects. The results do not support the idea of a simple parallel between autism and mediotemporal lobe amnesias. The visual memory performance of the autistic subjects was discussed in the light of the possibility of a subtle involvement of the mediotemporal brain structures and inflexible cognitive strategies poorly suited to encode novel information.

P300 assessment of anxiety effects on processing novel stimuli.

In the present experiment, event-related potentials (ERPs) were used to investigate the effect of anxiety on the attention to novel stimuli. A total of 16 healthy subjects participated in an experiment involving the anticipation of electric shocks. ERPs from 15 scalp sites were recorded in response to three types of auditory stimuli, and two attentional modes during threat and safe conditions. The three types of auditory stimuli were (1) frequent "standard" tones, (2) rare "target" tones, and (3) rare "novel" sounds. In the passive attentional mode, subjects passively listened to the stimuli. In the active attentional model, they had to Press a button in response to target tones. In each attentional mode, stimuli were presented under two conditions: threat (anticipation of shock) and safe (no-shock anticipation). P3 to the target stimuli was not affected by shock anticipation. The amplitude of P3 to the novel stimuli, however, was increased by the threat of shock in the passive but not in the active mode. The lack of impact of anxiety on P3 to the novel stimuli in the active mode is discussed.

Effects of threat of shock, shock electrode placement and darkness on startle.

Fear can be elicited by physically-presented explicit threat stimuli or by more static contextual stimuli that are not an immediate source of danger. Research in both humans and animals suggest that fear produced by these two types of stimuli represents separate processes mediated by different brain structures. The present study used the startle reflex methodology to examine affective responses elicited by an explicit threat cue signalling a period of shock anticipation and by two types of contextual stimuli; darkness and attaching the shock electrodes. As expected, shock anticipation potentiated startle (fear-potentiated startle). Startle was also facilitated by darkness and by the placement of shock electrodes. Further, darkness increased fear-potentiated startle to an explicit threat cue, but did not affect the facilitation of startle produced by attaching the shock electrodes. It is suggested that affective responses to contextual stimuli should be considered when investigating both normal and pathological fear.

Effects of rare non-target stimuli on brain electrophysiological activity and performance.

In order to assess the effects of non-target stimuli on task performance and electrophysiological activity, 16 subjects performed reaction time (RT) experiments under 3 conditions. In all conditions, subjects had to press a button upon detection of rare (15%) target stimuli (1600 Hz) presented among frequent (85%) non-target stimuli. The 3 conditions differed based on their non-target stimuli. In one condition, the non-targets consisted of 'standard' stimuli (900 Hz). In the two other conditions, rare and deviant non-target stimuli were randomly added to the standard stimuli. These deviant non-target stimuli consisted of either constant (700-Hz tones) or novel (buzzes, filtered noises and other unusual sounds) stimuli. Both the rare target and non-target stimuli elicited P300, responses. Behavioral (RT) and electrophysiological (event-related potential) data showed that stimuli that followed standard stimuli were processed differently compared to stimuli that followed deviant non-target stimuli. In the conditions containing deviant non-target stimuli, the P3b to the target stimuli was smaller and later, and the mean RT longer than in the condition with no deviant stimuli. These behavioral and electrophysiological changes induced by the deviant non-target stimuli were discussed with reference to two factors, distraction and increased level of task difficulty. It was suggested that each of these factors were differentially sensitive to the novelty of the rare deviant stimuli.

Effects of alcohol on baseline startle and prepulse inhibition in young men at risk for alcoholism and/or anxiety disorders.

OBJECTIVE: This study examined the hypothesis that a decreased reaction to alcohol and a deficit in prepulse inhibition (PPI) of the startle reflex are characteristics of male offspring of alcoholics without comorbid anxiety disorder. METHOD: Male offspring (N = 51) with a parental history of (1) alcoholism only, (2) anxiety disorder only, (3) alcoholism and anxiety disorder, and (4) no psychiatric disorder participated in an experiment examining the effects of alcohol on the acoustic startle reflex and on PPI. The experiment was carried out in two sessions in which subjects received an alcoholic beverage and placebo beverage on alternate days. RESULTS: The magnitude of startle was reduced by alcohol in each group. However, the degree of reduction was less in the offspring of alcoholics only compared to the other groups. In addition, PPI was reduced in the offspring of alcoholics only compared to the offspring of parents with no psychiatric disorder. CONCLUSIONS: A reduced reactivity to the effect of alcohol and a deficit in PPI might constitute vulnerability markers for alcoholism, but only in offspring of alcoholics without comorbid anxiety disorder.

Towards a wireless optical stimulation system for long term in-vivo experiments.

This paper presents our recent progresses towards the development of a wirelessly powered head mountable optical stimulator for enabling long-term optogenetic experiments with small freely moving transgenic models. The proposed system includes a wireless power transmission chamber with uniform power distribution in 3D and a wireless head mountable optical stimulator prototype with power recovery. The wireless power link, which includes the inductive chamber and power recovery circuits, is robust against subject movements in all directions, and against angular misalignment. Such link provides uniform power distribution without the need for a closed-loop control system, and can localize the transmitted power towards the receiver, without using additional detection and control circuitry compared to other systems. Additionally, the chamber is equipped with a camera for capturing the animal motion and behavior after applying optical stimulation patterns. A low-power microcontroller unit is embedded with the stimulator prototype to generate arbitrary light stimulation patterns. Measurement results show that the inductive chamber can continuously deliver 70 mW to the stimulator prototype with a power efficiency of 59%.

Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression.

Anhedonia--which is defined as diminished pleasure from, or interest in, previously rewarding activities-is one of two cardinal symptoms of a major depressive episode. However, evidence suggests that standard treatments for depression do little to alleviate the symptoms of anhedonia and may cause reward blunting. Indeed, no therapeutics are currently approved for the treatment of anhedonia. Notably, over half of patients diagnosed with bipolar disorder experience significant levels of anhedonia during a depressive episode. Recent research into novel and rapid-acting therapeutics for depression, particularly the noncompetitive N-Methyl-D-aspartate receptor antagonist ketamine, has highlighted the role of the glutamatergic system in the treatment of depression; however, it is unknown whether ketamine specifically improves anhedonic symptoms. The present study used a randomized, placebo-controlled, double-blind crossover design to examine whether a single ketamine infusion could reduce anhedonia levels in 36 patients with treatment-resistant bipolar depression. The study also used positron emission tomography imaging in a subset of patients to explore the neurobiological mechanisms underpinning ketamine's anti-anhedonic effects. We found that ketamine rapidly reduced the levels of anhedonia. Furthermore, this reduction occurred independently from reductions in general depressive symptoms. Anti-anhedonic effects were specifically related to increased glucose metabolism in the dorsal anterior cingulate cortex and putamen. Our study emphasizes the importance of the glutamatergic system in treatment-refractory bipolar depression, particularly in the treatment of symptoms such as anhedonia.

Conditioned inhibition of fear-potentiated startle and skin conductance in humans.

Conditioned inhibition of classical conditioning was investigated with the startle reflex and the skin conductance response (SCR) in humans using a serial presentation of the conditioned inhibitor (X) and of the conditioned stimulus (CS). The unconditioned stimulus (US) was a shock. During conditioning, participants were presented with two different reinforced CS (A, B) and with X preceding A (noted X-->A). During X-->A, A was not reinforced with the US. During the summation test, B, X-->B, and Y-->B were presented (Y was a new stimulus that tested the specificity of the inhibitory properties of X). B was not reinforced during the summation test. A, B, X, and Y were lights of different colors. Participants were divided into a low and a high anxious group based on the TPQ (C.R. Cloninger, 1987). In the low anxious group, conditioned startle potentiation and SCR responses to A were inhibited when X preceded A (noted A(XA)). This differential responding to A and A(XA) emerged earlier with the SCR than with startle. During the summation test, the inhibitory properties of X did not transfer to B. In the high anxious group, there was only a differential SCR to A and A(XA). X did not inhibit startle potentiation to A.