Francois Richer

Obstructive Sleep Apnea Syndrome: Pathogenesis of Neuropsychological Deficits

Neuropsychological deficits have been documented in patients with obstructive sleep apnea syndrome (OSAS). Both nocturnal hypoxemia and impairement of daytime vigilance have been suggested as the pathogenesis of these deficits, yet it remains difficult to find good correlations between cognitive deficits and either of these physiological parameters. In the present study, 10 normal controls were compared to 10 moderately and 10 severely apneic patients, all recorded in a sleep laboratory for two consecutive nights, with a vigilance and neuropsychological assessment made during the intervening day. Relative to the controls, moderate and severe OSAS showed differences in many cognitive functions, although the severely affected showed the greater differences. Moreover, severe apneics were also worse than moderate apneics on tests that were found to be normal in the latter group. This suggests a discontinuity in the appearance of neuropsychological deficits as OSAS progresses. Further analyses revealed that reductions in general intellectual measures, as well as in executive and psychomotor tasks were all attributable to the severity of hypoxemia, while other attention and memory deficits were related to vigiance impairment. Therefore, both vigilance impairment and nocturnal hypoxemia may differentially contribute to the cognitive dysfunctions found in OSAS.

Persistent neuropsychological deficits and vigilance impairment in sleep apnea syndrome after treatment with continuous positive airways pressure (CPAP)

The obstructive sleep apnea syndrome is characterized by nocturnal sleep disturbance, excessive daytime sleepiness and neuropsychological deficits in the areas of memory, attention, and executive tasks. In the present study, these clinical manifestations were assessed in apneic patients before and 6 months after treatment with nasally applied continuous positive airway pressure (CPAP). CPAP treatment was found to restore normal respiration during sleep and to normalize sleep organization. Daytime vigilance greatly improved with treatment but some degree of somnolence as compared to normal controls persisted. Similarly, most neuropsychological deficits normalized with treatment. The exception was for planning abilities and manual dexterity, two neuropsychological deficits that have been found to be highly correlated with the severity of nocturnal hypoxemia. These results raise the possibility that anoxic brain damage is a pathogenic factor in severe obstructive sleep apnea syndrome.

Detection and recognition: Concurrent processes in perception

In two experiments, event-related brain potentials (ERPs) were recorded while subjects performed a simultaneous detection and recognition task. Ten subjects listened to pure tones in noise and reported both whether a target tone had occurred (using a four-category confidence rating scale) and whether the target was one of two (Experiment 1) or four (Experiment 2) tones differing in frequency. The amplitudes of three ERP components were found to be differentially related to detection and recognition performance. The early N100 component varied with processing related only to detection, while the late P300 varied with both detection and recognition, and a later slow positive shift varied only with recognition and not with detection. While the latenciee of both N100 and P300 increased for less confident target detections, there were no differences in the latencies of these ERP components between correctly and incorrectly identiffed targets. Recognition performance was above the level expected by chance even when subjects reported that no target had been presented. The results indicate that brain potential components can be used to disclose temporal features of the processing of a stimulus by the nervous system and support the view that detection and recognition are partially independent, concurrent processes in perception.

Methods for separating temporally overlapping sources of neuroelectric data

SummaryThe localization of intracranial sources of EEG or MEG signals can be misled by the combined effect of several sources, as illustrated by simulated MEG data in which two of the three dipolar sources have slightly out of phase activity and partly complementary scalp topographies. These data were analysed by three different source localization methods. Fitting a single source to each sequential topography worked perfectly when only one source was active; this could also account for as much as 95% of the spatial variance of topographies resulting from two overlapping sources, although the solution was then far from any source. A principal component analysis approach followed by an oblique rotation (fitting one source to the spatial aspect of each component) correctly localized two of the sources but severely mislocated the source that was never active alone. Spatiotemporal source modeling (simultaneously fitting a set of sources to all consecutive topographies) correctly localized all three sources, provided that the parameter optimization method could escape sub-optimal local minima of the error function. Temporally overlapping sources can thus be separated and correctly identified if the mathematical model is adequate and the optimization procedure is well adapted.

Episodic memory impairment in Huntington's disease : A meta-analysis

Memory dysfunction is an important feature in the clinical presentation of Huntingtons disease (HD) and may precede the onset of motor symptoms. Although several studies have contributed to the quantitative and qualitative description of memory impairments in HD, the characterization of episodic memory impairments has varied considerably. Whereas most studies report significant impairments on free recall tests, performance on recognition tests has been considerably more variable, ranging from normal to markedly deficient. This absence of a well-established recognition memory deficit has led some investigators to attribute the memory deficits in HD to a retrieval-based episodic memory impairment. We felt that a quantitative review of the literature was needed to better characterize these episodic memory impairments. We conducted a meta-analysis to assess the magnitude of the recognition memory deficit in HD and to examine it in relation to the known deficit in recall. Memory data were provided by 544 symptomatic HD patients, 224 presymptomatic gene-carriers, and 963 control subjects. The overall group comparison between symptomatic patients and controls yielded effect sizes of d=1.95 for free recall and d=1.73 for recognition. We split the symptomatic group into two subgroups based on their mental status (mild and moderate/severe dementia) and both showed significant deficits in recall and recognition memory, though recall was more impaired than recognition in the mild dementia subgroup. Only slight memory impairment was observed in the presymptomatic subjects. The results show that deficits in recognition memory must be accounted for in future models of memory impairment in HD.

Tourette syndrome and dopaminergic genes: a family-based association study in the French Canadian founder population.

Tourette syndrome (TS) is a genetically complex disorder for which no causative genes have been unequivocally identified. Nevertheless, a number of molecular genetic studies have investigated several candidate genes, particularly those implicated in dopamine modulation. The results of these studies were inconclusive, which may be due, at least in part, to the variable ethnicity of the patients included in different studies and the chosen research design. In this study, we used a family-based association approach to investigate the implication of dopamine-related candidate genes, which had been previously reported as possibly associated with TS [genes that encode for the dopamine receptors DRD2, DRD3 and DRD4, the dopamine transporter 1 (SLC6A3) and the monoamine oxidase-A (MAO-A). The studied group was composed of 110 TS patients. These patients were selected from the French Canadian population, which displays a founder effect. Excess transmission of the 7-repeat allele of the DRD4 exon-3 VNTR polymorphism (χ2 TDT =4.93, 1 df, P=0.026) and the putative ‘high-activity’ alleles of the MAO-A promoter VNTR polymorphism (χ2 TDT =7.124, 1 df P=0.0076) were observed. These results were confirmed in a subgroup of patients with no attention deficit/hyperactivity or obsessive compulsive comorbid disorders. Haplotype analysis using one or two supplemental polymorphism in each of these genes confirmed these associations and allowed one to identify risk haplotypes. No associations were found for DRD2, DRD3 or SLC6A3. These data support the notion that DRD4 and MOA-A genes may confer an increased risk for developing TS in the French Canadian population.

Target Detection Deficits in Frontal Lobectomy

We examined the hypothesis of dorsomedial frontal lobe involvement in target detection through the effects of distractor interference and multiple target interference on unilateral lobectomy patients. Seven patients who underwent a unilateral frontal lobectomy for epilepsy involving dorsomedial cortex and variable amounts of lateral cortex were compared to 10 patients with a unilateral temporal lobectomy and to 10 normal adults on a visual character cancellation task. The task involved detecting occurrences of target characters embedded in rows of characters under three conditions: detection of one target character in the absence of distractors, detection of one target character among distractors, and detection of three targets among distractors. Visual detection performance was compared to that in the Stroop reading interference task. Frontals were predictably slower than the other groups in the baseline conditions of the character cancellation task and the Stroop task. After partialing out baseline detection performance in the character cancellation task, frontals showed an almost normal detection in the presence of distractors but were distinctly slower and made more errors than the other groups in multiple target detection. Frontals were also slower on the Stroop even after partialing out baseline naming performance. Temporals were normal on all tasks. Results suggest that frontal damage can affect selectivity in target detection as well as the Stroop and that this deficit is independent of the general psychomotor slowing observed in these patients.

Human intracerebral potentials associated with target, novel, and omitted auditory stimuli

SummaryWe recorded late auditory potentials from lateral and medial regions in the frontal, temporal and parietal lobes of patients with temporal lobe epilepsy implanted with horizontal depth electrodes. Tone sequences were presented in three tasks: 1) auditory target detection in a tone sequence, 2) target detection with interspersed novel stimuli, and 3) detection of stimulus omissions. At frontal sites, potentials to targets showed a triphasic response with peak latencies around 200, 270 and 350 ms. At temporal sites, potentials consisted of a generally positive 285 ms peak which was sometimes accompanied by a negative peak at 200 ms or at 400 ms. At parietal sites, potentials were generally triphasic with latencies of about 230, 300, and 370 ms. At most sites, potentials evoked by novel stimuli had shorter latencies than those evoked by targets. The frontal and parietal potentials were either absent or strongly attenuated during stimulus omissions. The results lend further support to the multiple generator hypothesis of late potentials and suggest that some of the cerebral sources of the late potentials are stimulus dependent while others are not.

RESPONSE SELECTION DEFICITS IN FRONTAL EXCISIONS

We compared the performance of patients with frontal excisions, patients with temporal excisions and controls in tasks involving speeded choice responses in which a number of variables were manipulated including: perceptual difficulty, stimulus and response set-size, associative complexity, and spatial stimulus-response compatibility. Response times were sensitive to all manipulations but did not show any group differences. The error rates of the three groups were equally affected by perceptual difficulty and response set-size but frontals were preferentially affected by spatial S-R compatibility, associative complexity, and the number of stimuli per response. The results are consistent with a basic deficit in response selection processes which could underly many problems produced by frontal lesions.

Neural correlates of dual task interference in rapid visual streams: An fMRI study

In rapid streams of visual stimuli, identification of a first target interferes with identification of a second target presented within the next half second (the attentional blink or AB). It has been suggested that rapid perceptual decisions under masking interference involve interactions between frontal and posterior cortex. We investigated the neural correlates of the AB using functional magnetic resonance imaging (fMRI). Twelve subjects viewed rapid streams of black letters in which were embedded two white target letters (T1 and T2) separated by either 300 or 700 ms. As expected, fewer correct T2 identifications were observed in the short-delay condition. Corresponding fMRI statistical images showed increased activation in inferotemporal and posterior parietal cortex, but also in lateral frontal cortex and cerebellum in the short-delay condition suggesting that these brain regions are associated with perceptual decisions under masking interference.