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Biomedical subjects

Michael M Saling

Publications and source records attributed to Michael M Saling.

At least 19 recordsLinked to original sources

Neurological control of human sexual behaviour: insights from lesion studies.

We review the human literature examining the effects of neurological insult on human sexual behaviour. We provide a synthesis of the findings to date, and identify key brain regions associated with specific aspects of human sexual behaviour. These include subcortical and cortical regions, with the mesial temporal lobe and the amygdala in particular being a crucial structure in the mediation of human sexual drive.

Amygdala↗

Long-term cognitive transitions, rates of cognitive change, and predictors of incident dementia in a population-based first-ever stroke cohort.

BACKGROUND AND PURPOSE: There are few data on long-term cognitive outcomes after first-ever stroke. We aimed to study long-term cognitive transitions, rates of cognitive change, and factors associated with incident dementia and cognitive impairment-no dementia (CIND) 2 years after first-ever stroke. METHODS: A population-based cohort of incident first-ever stroke cases (n=99; mean age, 69.9 years) and an age- and sex-matched comparison group (nonstrokes, n=99) were followed up for 2 years by 3 serial examinations. Rates of cognitive change were compared by repeated-measures analyses. Factors associated with incident dementia and CIND at 2 years were determined by multinomial logistic regression. RESULTS: Significant stroke x time interactions were present for all cognitive domains, with stroke cases showing a greater rate of decline compared with nonstrokes. Stroke recurrence during follow-up was responsible for significantly greater global decline. Strokes with recurrence (P=0.02), age (P=0.004), and baseline cognitive impairment (P<0.001) were independently associated with incident dementia at 2 years. Strokes without recurrence (P=0.008), age (P=0.001), and baseline cognitive impairment (P<0.001) were independently associated with CIND at 2 years. CONCLUSIONS: Recurrent stroke contributes importantly to global cognitive decline after a first-ever stroke. Secondary stroke prevention will be important in ameliorating dementia related to stroke. Mechanisms underlying the progression of early cognitive impairment to dementia in stroke patients need further investigation.

Adult↗

Cerebrovascular disease and dementia.

Cerebrovascular disease and dementia are extremely prevalent and disabling disorders affecting older people. Results of previous pathological investigations and later epidemiological studies have raised the possibility that the two disorders may be causally related. The study of such causal associations may provide insights that could lead to the development of strategies intended to prevent or treat dementia more effectively. Cerebrovascular disease has many manifestations, some of which are strong causal factors in the development of a future dementia. However, uncertainty and controversy exist regarding the presence and nature of the causal contribution of others. Potential therapeutic strategies for dementia are hindered by the lack of understanding of such relationships and the consequent difficulty in identifying a clear phenotype of dementia occurring predominantly due to cerebrovascular disease. The field is ripe for further examination of the associations between vascular factors and dementia, and the mechanisms underlying such associations. The interface between basic and clinical science has much to offer in clarifying the relationships between aging, vascular factors and cognitive decline in older people. In this review, we will attempt to synthesize data available from epidemiological, clinical and basic science research in the field of dementia related to cerebrovascular disease, highlighting potential avenues for further research.

Journal Article↗

Functional connectivity networks are disrupted in left temporal lobe epilepsy.

OBJECTIVE: Functional connectivity maps the distributed network of brain regions fluctuating synchronously during a continuous brain state. This study sought to investigate whether patients with left temporal lobe epilepsy (TLE) differ from controls in their resting-state functional connectivity between typical language regions. METHODS: We studied 17 patients with left TLE, together with eight healthy controls, using seeded functional connectivity. Seed regions were defined using the regions of maximal activation and deactivation during a language functional magnetic resonance imaging (fMRI) task in a separate cohort of 30 controls. RESULTS: Language fMRI produced the expected activation pattern, which was not different between patients and controls. However, functional connectivity between language areas during rest was markedly different; whereas controls showed connectivity between each of the seed areas and the majority of the language areas, patients showed connectivity only with a few areas, particularly the seed area itself. This difference was significant in the direct comparison of patients and control connectivity maps. INTERPRETATION: We suggest that this reduced connectivity in left temporal lobe epilepsy may reflect a disturbance of the language network during resting state in patients and may be related to subtle language difficulties in this patient population.

Adult↗

The validity of brief screening cognitive instruments in the diagnosis of cognitive impairment and dementia after first-ever stroke.

INTRODUCTION: Brief cognitive tests such as the Mini-mental State Examination (MMSE) and the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) have been used to detect cognitive impairment and dementia in studies of stroke patients. However, there are few data on their validity for such use. We have evaluated their validity in detecting cognitive impairment not dementia (CIND) and dementia in a community-based sample of first-ever stroke patients. METHODS: The standardized MMSE (S-MMSE) and the 16-item IQCODE were administered to 79 patients 1 year after a first-ever stroke. CIND and dementia were diagnosed independently using a comprehensive cognitive battery. The performances of the two tests were evaluated using receiver operating characteristic (ROC) analyses. Combined performance was evaluated when their scores were used in parallel (the "or rule"), in series (the "and rule") or as a weighted sum (the "weighted sum rule"). RESULTS: Both tests were extremely poor at detecting CIND individually and in combination. For dementia, at traditional cut-points, the S-MMSE (< or =23) was insensitive (0.50, 95% CI 0.16-0.84) and the IQCODE (> or =3.30) nonspecific (0.63, 95% CI 0.51-0.75). An acceptable balance between sensitivity and specificity was achieved for dementia using the "or rule" combination, but with only modest positive predictive value. CONCLUSIONS: The S-MMSE and the IQCODE were individually poor at detecting CIND and dementia after a nonaphasic first-ever stroke. The combination was useful in detecting dementia but it does not replace the need for detailed neuropsychological tests.

Aged↗

Is language lateralization in temporal lobe epilepsy patients related to the nature of the epileptogenic lesion?

PURPOSE: Early acquired lesions are considered to be a risk factor for atypical language lateralization in epilepsy, whereas developmental lesions are not. Hippocampal sclerosis (HS) can be understood as an early, acquired lesion, whereas developmental tumors (DT) are thought to originate in utero. We assessed whether language lateralization differs between these groups of temporal lobe epilepsy patients. METHODS: We used 3-Tesla functional MRI (fMRI) to assess 41 patients (16 DT, 25 HS) and 50 controls, performing a noun-verb-generation task. fMRI data were processed by using SPM2. A laterality index (LI) was calculated based on the number of activated voxels in left- and right-sided frontal lobe language areas. Atypical lateralization was considered if the index was < or = 0.2. RESULTS: Patients had a lower LI (0.42 +/- 0.5) than controls (0.6 +/- 0.3; p < or = 0.05), but the LI was not different between DT (0.44 +/- 0.5) and HS patients (0.43 +/- 0.4; p = 0.9). The frequency of atypical lateralization was increased in patients (27%) compared with controls (8%) but was similar in both patient groups (DT, 31%; HS, 24%). HS patients had an earlier onset and longer duration of epilepsy and a higher frequency of significant antecedent events (p < or = 0.05). CONCLUSIONS: Patients with TLE demonstrate a deviation toward atypical language lateralization. However, language lateralization was not different between patients with presumably acquired lesions compared with patients with developmental pathology. This suggests that the nature of the temporal lobe lesion does not influence overall language lateralization.

Adult↗

FMRI lateralization of expressive language in children with cerebral lesions.

PURPOSE: Lateralization of language function is crucial to the planning of surgery in children with frontal or temporal lobe lesions. We examined the utility of functional magnetic resonance imaging (fMRI) as a determinant of lateralization of expressive language in children with cerebral lesions. METHODS: fMRI language lateralization was attempted in 35 children (29 with epilepsy) aged 8-18 years with frontal or temporal lobe lesions (28 left hemisphere, five right hemisphere, two bilateral). Axial and coronal fMRI scans through the frontal and temporal lobes were acquired at 1.5 Tesla by using a block-design, covert word-generation paradigm. Activation maps were lateralized by blinded visual inspection and quantitative asymmetry indices (hemispheric and inferior frontal regions of interest, at p<0.001 uncorrected and p<0.05 Bonferroni corrected). RESULTS: Thirty children showed significant activation in the inferior frontal gyrus. Lateralization by visual inspection was left in 21, right in six, and bilateral in three, and concordant with hemispheric and inferior frontal quantitative lateralization in 93% of cases. Developmental tumors and dysplasias involving the inferior left frontal lobe had activation overlying or abutting the lesion in five of six cases. fMRI language lateralization was corroborated in six children by frontal cortex stimulation or intracarotid amytal testing and indirectly supported by aphasiology in a further six cases. In two children, fMRI language lateralization was bilateral, and corroborative methods of language lateralization were left. Neither lesion lateralization, patient handedness, nor developmental versus acquired nature of the lesion was associated with language lateralization. Involvement of the left inferior or middle frontal gyri increased the likelihood of atypical language lateralization. CONCLUSIONS: fMRI lateralizes language in children with cerebral lesions, although caution is needed in interpretation of individual results.

Adolescent↗

Characterizing psychosocial outcome trajectories following seizure surgery.

PURPOSE: We have developed a new approach to characterizing psychosocial outcome after seizure surgery that allows us to identify diverse individual trajectories as well as subgroups of patients with similar outcomes. METHODS: Eighty-nine anterior temporal lobectomy (ATL) patients were recruited through our Seizure Surgery Follow-up and Rehabilitation Program. The Austin CEP Interview was used to measure psychosocial adjustment presurgery, at discharge, and 1, 3, 6, 12, and 24 months postsurgery. Patient outcome trajectories were characterized across this time frame using a profile-focused form of dual clustering that leads to a lattice representation. RESULTS: Two major, distinct outcome subgroups were identified. Fifty-eight percent (58%) of patients reported good outcomes, characterized by improved family dynamics, enhanced vocational and social functioning, and driving by 24 months postsurgery. A range of trajectories led to these outcomes, including the experience of early postoperative adjustment difficulties. In contrast, 31% of patients perceived their outcomes as poor, reporting affective disturbance at 12 months and difficulties discarding sick role behaviors. Early anxiety served as a marker of poor outcomes, while resolution of early anxiety and vocational change at 12 months were indicators of good outcomes at 24 months. The remaining 11% of patients reported minimal adjustment features. CONCLUSIONS: For the majority of patients, seizure surgery gives rise to an evolving process of postoperative adjustment that leads to distinct outcome trajectories. Our approach questions the clinical sensitivity of health-related quality of life measures that average across patients to provide a unitary measure of outcome. Although preliminary, the findings have implications for postoperative treatment, including the identification of markers of longer-term outcomes.

Adaptation, Psychological↗

Cerebrovascular disease and dementia.

Cerebrovascular disease and dementia are extremely prevalent and disabling disorders affecting older people. Results of previous pathological investigations and later epidemiological studies have raised the possibility that the two disorders may be causally related. The study of such causal associations may provide insights that could lead to the development of strategies intended to prevent or treat dementia more effectively. Cerebrovascular disease has many manifestations, some of which are strong causal factors in the development of a future dementia. However, uncertainty and controversy exist regarding the presence and nature of the causal contribution of others. Potential therapeutic strategies for dementia are hindered by the lack of understanding of such relationships and the consequent difficulty in identifying a clear phenotype of dementia occurring predominantly due to cerebrovascular disease. The field is ripe for further examination of the associations between vascular factors and dementia, and the mechanisms underlying such associations. The interface between basic and clinical science has much to offer in clarifying the relationships between aging, vascular factors and cognitive decline in older people. In this review, we will attempt to synthesize data available from epidemiological, clinical and basic science research in the field of dementia related to cerebrovascular disease, highlighting potential avenues for further research.

Aging↗

The amygdala and sexual drive: insights from temporal lobe epilepsy surgery.

The aim of this study was to explore the relationship between the amygdala and human sex drive. We compared amygdalar volume in groups of patients with or without sexual changes after temporal lobe resection and in age-matched neurologically normal subjects. Forty-five patients with intractable temporal lobe epilepsy who underwent surgical resection in the Comprehensive Epilepsy Program at the Austin and Repatriation Medical Centre completed a semistructured interview and questionnaire relating to sexual outcome after surgery. Volumetric analyses of both amygdalae were conducted on the patients' preoperative T(1)-weighted magnetic resonance imaging scans and those of 46 neurologically normal controls. Patients who reported a postoperative sexual increase had a significantly larger amygdalar volume contralateral to the site of their resective surgery than patients with a sexual decrease or no change than control subjects. There was a significant positive relationship between contralateral amygdalar volume and the maximum degree of sexual change. We have demonstrated a relationship between contralateral amygdalar volume and sexual outcome in patients undergoing temporal lobe resection. This finding provides evidence for an important role of the amygdala in regulating human sexual behavior. A larger contralateral amygdala may contribute to the expression of increased or improved sexuality after temporal lobe resection.

Adult↗

A high-field functional MRI study of quadri-lingual subjects.

We assessed six multilingual subjects by functional MRI using a Noun Verb Generation task in four different languages. We hypothesised that the degree of proficiency in each language would be related to the extent of functional activity measured in a region of interest analysis. Proficiency in each language was quantified using two neuropsychological tests. All four languages activated overlapping brain areas, corresponding to the major language regions. The number of activated voxels correlated with proficiency, so that the activated volume increased for languages in which a subject had poorer proficiency. Activation did not appear to be dependent on the age at which the language was learnt.

Adult↗

Paradoxical results in the cure of chronic illness: the "burden of normality" as exemplified following seizure surgery.

Little has been written about processes of recovery following life-changing medical interventions for chronic illness. This article reviews our research with chronic epilepsy patients undergoing neurosurgery for the relief of intractable partial seizures. This research has given rise to a new conceptualization of adjustment and outcome following effective treatment of chronic illness, representing the first, detailed characterization of this process from a psychological and psychosocial perspective. Crucial to outcome are patient and family expectations prior to treatment, and learning to discard roles associated with chronic illness after treatment. These and the posttreatment affective functioning of the patient temper the view of medical outcome, and can account for paradoxical clinical effects, such as worsening patient psychosocial functioning in the context of medical treatment success. Our results have clear implications for the clinical management of chronically ill patients and their families to optimize treatment outcome.

Adaptation, Psychological↗

Subtle microscopic abnormalities in hippocampal sclerosis do not predict clinical features of temporal lobe epilepsy.

PURPOSE: Subtle microdysplastic features are found in some patients with hippocampal sclerosis (HS) and refractory temporal lobe epilepsy. The significance of these findings is unknown. We investigated their frequency, relation to the pattern of HS, and clinical associations. METHODS: One-hundred forty patients with histologically confirmed HS (mean age at operation, 35 years; 85 women) were analyzed. The presence of HS and subtle structural abnormalities (SSAs) in the mesial temporal lobe and in the lateral neocortical tissue was assessed in detail. Antecedents, seizure characteristics, two verbal memory tests, and outcome in HS patients with and without SSAs were determined. RESULTS: SSAs were found in 60 (43%) of the 140 HS patients, being mesial only in 32 of the 60 cases, and lateral only in nine cases; the remaining 19 cases had both mesial and lateral abnormalities. The frequency of SSA was not related to the pattern of HS or other tested variables. Prolonged febrile convulsions were present in 26 (44%) patients with SSAs, and in 26 (34%) patients (not significant) without SSAs. The outcome after surgery did not differ between patients with SSAs (incidence rate ratio for seizure recurrence, 0.9; 95% confidence interval, 0.5-1.6) compared with patients without SSAs (reference ratio, 1). CONCLUSIONS: Forty-three percent of HS patients have SSAs in their lobectomy specimens. The presence of SSAs does not predict clinical characteristics, such as presence of prolonged febrile convulsions, postsurgical outcome, or neuropsychological performance, nor does it correlate with the histologic pattern of HS.

Adult↗

Increased risk of cognitive impairment 3 months after mild to moderate first-ever stroke: a Community-Based Prospective Study of Nonaphasic English-Speaking Survivors.

BACKGROUND AND PURPOSE: Results of hospital-based studies indicate a high risk of cognitive impairment 3 months after stroke. There are no comprehensive data on this issue from prospective community-based studies comparing first-ever stroke patients with stroke-free subjects. METHODS: We administered a comprehensive neuropsychological battery to 99 community-based nonaphasic survivors of first-ever stroke at 3 months and 99 age- and sex-matched (1:1) stroke-free individuals. Domain-specific cognitive deficits were identified by blinded neuropsychological consensus. METHODS: Stroke patients were more likely to suffer any cognitive impairment (relative risk [RR], 1.5; 95% CI, 1.1 to 2.1) attributable mainly to a greater risk of single-domain cognitive impairment (RR, 2.8; 95% CI, 1.5 to 5.3) but not multiple-domain cognitive impairment (RR, 1.2; 95% CI, 0.8 to 1.9). CONCLUSIONS: In this community-based study, a first-ever stroke of mild to moderate severity was associated with a significant risk of cognitive impairment at 3 months, even in the absence of clinical aphasia. This was due primarily to an increased risk of solitary deficits rather than generalized deficits.

Adult↗

Sexual outcome after epilepsy surgery.

The aim of this study was to provide a description of patient-perceived sexual change after temporal lobe resection (TLR) and extratemporal resection (ETR). Fifty-eight TLR and sixteen ETR patients completed a semistructured interview and questionnaire assessing sexual change after epilepsy surgery. Five areas of sexual functioning were addressed: sexual drive, thoughts/fantasies, interest, masturbation, and activity. Each patient's perception of sexual changes relative to perceived levels of normal functioning was assessed. Characteristically, the onset of sexual change occurred in the first three postoperative months and persisted to the time of interview. A postoperative sexual change was significantly more likely to be reported by patients who had undergone TLR (64%) than ETR (25%). In the TLR group, sexual change was significantly more frequent following right-sided resections. Marked sexual change occurred more frequently in females than males. Postoperative sexual change is an important outcome feature after epilepsy surgery. The predisposition of TLR patients to postoperative change provides further evidence for a temporal lobe contribution to sexual function.

Adolescent↗

Correlation between language organization and diffusion tensor abnormalities in refractory partial epilepsy.

PURPOSE: Atypical language organization is more frequently found in patients with refractory partial epilepsy than in healthy controls; however, the reasons for this are not well known. Here we assess the relation between language laterality index (LI) and white-matter tract changes. METHODS: Nine patients with refractory partial epilepsy were assessed with a 3-T GE scanner. Functional magnetic resonance imaging (fMRI) of language and diffusion tensor imaging (DTI) were acquired. For the fMRI, a noun-verb generation task was performed, all images were motion corrected, and activated pixels in classic language areas were counted. The DTI images were acquired in six standard directions with an initial non-diffusion-weighted scan. The "average anisotropy" was determined in a region of interest in the frontal lobe, temporal lobe, and parietal lobe white matter. An asymmetry index (AI) was calculated for language and DTI. Atypical language lateralization was diagnosed if the lateralization index (LI)-language was smaller than 0.4. RESULTS: Two of the nine patients had atypical language localization (LI-language, -0.6, and 0.3); both had left temporal DTI asymmetry (LI-DTI, -0.3 and -0.2). The remaining seven patients had typical language localization, and no marked DTI abnormalities. Asymmetry in temporal lobe DTI correlated with LI-language (r= 0.8; p = 0.006). CONCLUSIONS: Atypical language lateralization in patients with partial epilepsy may be associated with white-matter tract abnormalities.

Adolescent↗

Verbal memory in left temporal lobe epilepsy: evidence for task-related localization.

We explored the hypothesis that components of verbal memory are subserved by separate temporal lobe structures in patients with temporal lobe structures in patients with temporal lobe epilepsy [correction]. Uptake of 18F-fluorodeoxyglucose (FDG) measured by positron emission tomography, hippocampal volume, and memory for arbitrarily and semantically related verbal paired associates were examined in 27 patients with left temporary lobe epilepsy. Scores from memory tests performed outside the scanner were regressed against normalized resting FDG uptake at each voxel. Significant regression was seen in the left perirhinal cortex (Talaraich coordinates x, y, z: -29, 10, -34; p < 0.05) for arbitrarily related word pairs. For semantically related paired associates, significant regression was present in the left inferior temporal gyrus (x, y, z: -48, -18, -24; p < 0.05). In subsequent analyses, mean FDG uptake within a spherical region of interest centered on the perirhinal peak predicted performance on both tasks. Mean FDG uptake in a region of interest centered on the inferior temporal peak made an additional, independent contribution to memory for semantically related pairs. Hippocampal volumes did not explain any additional variance in memory scores. Our findings indicate that heterogeneity in the left temporal lobe structures mediating verbal memory function, and support the view that the perirhinal cortex is an important mnemonic substrate.

Adolescent↗

Direct and indirect measures of verbal relational memory following anterior temporal lobectomy.

Medial temporal lobe (MTL) structures are implicated in forming conjunctions between events in order to form enduring relational memories; these memories are not evident using direct measures with varieties of amnesic subjects. Extratemporal brain structures are thought to be responsible for preserved memories, which are sometimes detectable using indirect measures. The present study tests this theory of multiple memory systems by examining whether preserved learning can be demonstrated for relational material in MTL-disordered subjects using an indirect measure which minimises conscious mediation of performance. The subjects had undergone anterior temporal lobectomy for relief of temporal lobe epilepsy: left-sided (LATL) cases had a mild verbal amnesia and right-sided (RATL) cases had better verbal memory, forming a comparison group. A direct measure of verbal relational memory was provided by successive trials of cued recall in a specially-constructed paired associate learning task with arbitrarily paired words; pairs consisted of either concrete or abstract words. LATL subjects performed worse than RATL subjects, and particularly so with abstract words. Following direct testing, memory for the pairings was measured indirectly using a masked recognition priming technique. RATL subjects showed savings in RT, demonstrating that masked priming can reveal evidence of the formation of conjunctions. Critically, LATL subjects showed no evidence of preserved learning with priming. Thus when MTL structures are damaged, relational memory appears to be affected without exception, consistent with the tenets of multiple memory systems theory.

Adult↗