Terra incognita—cerebellar contributions to neuropsychiatric and cognitive dysfunction in behavioral variant frontotemporal dementia

Although converging evidence has positioned the human cerebellum as an important relay for intact cognitive and neuropsychiatric processing, changes in this large structure remain mostly overlooked in behavioral variant frontotemporal dementia (bvFTD), a disease which is characterized by cognitive and neuropsychiatric deficits. The present study assessed whether degeneration in specific cerebellar subregions associate with indices of cognition and neuropsychiatric performance in bvFTD. Our results demonstrate a relationship between cognitive and neuropsychiatric decline across various domains of memory, language, emotion, executive, visuospatial function, and motivation and the degree of gray matter degeneration in cerebellar lobules V–VII. Most notably, bilateral cerebellar lobule VII and the posterior vermis emerged as distinct for memory processes, the right cerebellar hemisphere underpinned emotion, and the posterior vermis was highlighted in language dysfunction in bvFTD. Based on cortico-cerebellar connectivity maps, these findings in the cerebellum are consistent with the neural connections with the cortices involved in these domains in patients with bvFTD. Overall, the present study underscores the significance of cortical-cerebellar networks associated with cognition and neuropsychiatric dysfunction in bvFTD

Ventilatory Phenotypes among Four Strains of Adult Rats.

Our purpose in this study was to identify different ventilatory phenotypes among four different strains of rats. We examined 114 rats from three in-house, inbred strains and one outbred strain: Brown Norway (BN;n = 26), Dahl salt-sensitive (n = 24), Fawn-hooded Hypertensive (FHH: n = 27), and outbred Sprague-Dawley rats (SD; n = 37). We measured eupneic (room air) breathing and the ventilatory responses to hypoxia (12% O2-88% N2), hypercapnia (7% CO2), and two levels of submaximal exercise. Primary strain differences were between BN and the other strains. BN rats had a relatively attenuated ventilatory response to CO2 (P \u3c 0.001), an accentuated ventilatory response to exercise (P \u3c 0.05), and an accentuated ventilatory roll-off during hypoxia (P \u3c 0.05). Ventilation during hypoxia was lower than other strains, but hyperventilation during hypoxia was equal to the other strains (P \u3e 0.05), indicating that the metabolic rate during hypoxia decreased more in BN rats than in other strains. Another strain difference was in the frequency and timing components of augmented breaths, where FHH rats frequently differed from the other strains, and the BN rats had the longest expiratory time of the augmented breaths (probably secondary to the blunted CO2 sensitivity). These strain differences not only provide insight into physiological mechanisms but also indicate traits (such as CO2 sensitivity) that are genetically regulated. Finally, the data establish a foundation for physiological genomic studies aimed at elucidating the genetics of these ventilatory control mechanisms

Determining the Impact of Autobiographical Experience on "Meaning": New Insights from Investigating Sports-related Vocabulary and Knowledge in Two Cases with Semantic Dementia

Snowden, Griffiths, and Neary (1994, 1995) have proposed thatautobiographical experience helps to maintain the integrity of semantic memory in patients with semantic dementia. We investigated this hypothesis by testing knowledge related to golf and bowls in two case studies. If Snowden and colleagues' hypothesis is correct, our two patients should have better semantic knowledge for the sport that they regularly experience, compared with knowledge of other sports. In keeping with Snowden et al's hypothesis, we found that autobiographical experience influenced the ability of the patients to match up a surname with a first name: The names of personally and currently relevant golf bowls partners were more likely to be matched correctly than such personally relevant names from the past, or the names of famous sports celebrities. Unlike Snowden et al., however, we found that knowledge of people, in all categories, was severely impoverished and that any semantic information was produced as part of an autobiographical memory. Likewise, detailed study of each patient's understanding of their favourite sportrevealed no significanteffectof autobiographical experience on true semantic knowledge. We propose that the ability of semantic dementia patients to encode, albeit temporarily, recent autobiographical memories via a spared hippocampal complex supports the production of highly autobiographically constrained semantic-like facts and, to a lesser extent, frequently encountered names. There is, however, no direct effect of autobiographical experience on previously established semantic memory, i.e. knowledge of golf, bowls, and people, presumably stored within the temporal neocortex. These results are discussed with respect to current anatomically based computational models of long-term memory

A questionable semantics: The interaction between semantic knowledge and autobiographical experience in semantic dementia

In our earlier article, we proposed that recent episodic experiences in patients with semantic dementia support the production of nongeneralisable, autobiographically constrained, “semantic-like” facts (Graham, Lambon Ralph, & Hodges, 1997). We argued that this type of “semantic-like” knowledge was distinguishable from true semantic information because our two patients with semantic dementia showed no facilitatory effect of recent autobiographical experiences on their knowledge of golf and bowls; information which was presumably learnt prior to the onset of their disease. In this paper, we discuss the implications of these results for current views relating to the nature and organisation of long-term memory

Characterizing sexual behavior in frontotemporal dementia

Background: Frontotemporal dementia (FTD) is characterized by a number of prominent behavioral changes. While FTD has been associated with the presence of aberrant or unusual sexual behaviors in a proportion of patients, few studies have formally investigated changes in sexual function in this disease. Objective: We aimed to systematically quantify changes in sexual behavior, including current symptoms and changes from prior diagnoses, in behavioral-variant (bvFTD) and semantic dementia (SD), compared to Alzheimer’s disease (AD). Methods: Carers of 49 dementia patients (21 bvFTD, 11 SD, 17 AD) were interviewed using the Sexual Behavior and Intimacy Questionnaire (SIQ), a survey designed to assess changes in sexual function across multiple domains including initiating, level of affection, and aberrant or unusual sexual behavior. Results: BvFTD patients show prominent hyposexual behavior including decreased affection, initiation, and response to advances by partners, and decreased frequency of sexual relations, compared to AD and to SD patients. The greatest changes in sexual behavior compared to pre-diagnoses were found in the bvFTD group with a 90–100% decrease in initiation, response, and frequency of sexual relations. Notably, aberrant or unusual sexual behavior was reported in a minority of bvFTD and SD patients and occurred in patients who also showed hyposexual behavior toward their partner. Conclusion: Overall loss of affection, reduced initiation of sexual activity, and responsiveness is an overwhelming feature of bvFTD. In contrast, aberrant or unusual sexual behavior is observed in the minority of bvFTD patients. The underlying pathophysiology of these changes likely reflects structural and functional changes in frontoinsular and limbic regions including the hypothalamus

Comparison of location, depth, quality and intensity of experimentally induced pain in six low back muscles

Introduction: The pattern of pain originating from experimentally induced low back pain appears diffuse. This may be because sensory information from low back muscles converges, sensory innervation extends over multiple vertebral levels, or people have difficulty accurately representing the painful location on standardized pain maps

Effects on Breathing of Agonists to μ-opioid or GABA\u3csub\u3eA\u3c/sub\u3e Receptors Dialyzed into the Ventral Respiratory Column of Awake and Sleeping Goats

Pulmonary ventilation (V̇I) in awake and sleeping goats does not change when antagonists to several excitatory G protein-coupled receptors are dialyzed unilaterally into the ventral respiratory column (VRC). Concomitant changes in excitatory neuromodulators in the effluent mock cerebral spinal fluid (mCSF) suggest neuromodulatory compensation. Herein, we studied neuromodulatory compensation during dialysis of agonists to inhibitory G protein-coupled or ionotropic receptors into the VRC. Microtubules were implanted into the VRC of goats for dialysis of mCSF mixed with agonists to either μ-opioid (DAMGO) or GABAA (muscimol) receptors. We found: (1) V̇I decreased during unilateral but increased during bilateral dialysis of DAMGO, (2) dialyses of DAMGO destabilized breathing, (3) unilateral dialysis of muscimol increased V̇I, and (4) dialysis of DAMGO decreased GABA in the effluent mCSF. We conclude: (1) neuromodulatory compensation can occur during altered inhibitory neuromodulator receptor activity, and (2) the mechanism of compensation differs between G protein-coupled excitatory and inhibitory receptors and between G protein-coupled and inotropic inhibitory receptors

State-Dependent and -Independent Effects of Dialyzing Excitatory Neuromodulator Receptor Antagonists into the Ventral Respiratory Column

Unilateral dialysis of the broad-spectrum muscarinic receptor antagonist atropine (50 mM) into the ventral respiratory column [(VRC) including the pre-Bötzinger complex region] of awake goats increased pulmonary ventilation (V̇i) and breathing frequency (f), conceivably due to local compensatory increases in serotonin (5-HT) and substance P (SP) measured in effluent mock cerebral spinal fluid (mCSF). In contrast, unilateral dialysis of a triple cocktail of antagonists to muscarinic (atropine; 5 mM), neurokinin-1, and 5-HT receptors does not alter V̇i or f, but increases local SP. Herein, we tested hypotheses that 1) local compensatory 5-HT and SP responses to 50 mM atropine dialyzed into the VRC of goats will not differ between anesthetized and awake states; and 2) bilateral dialysis of the triple cocktail of antagonists into the VRC of awake goats will not alter V̇i or f, but will increase local excitatory neuromodulators. Through microtubules implanted into the VRC of goats, probes were inserted to dialyze mCSF alone (time control), 50 mM atropine, or the triple cocktail of antagonists. We found 1) equivalent increases in local 5-HT and SP with 50 mM atropine dialysis during wakefulness compared with isoflurane anesthesia, but V̇i and f only increased while awake; and 2) dialyses of the triple cocktail of antagonists increased V̇i, f, 5-HT, and SP