Comments on energy conservation treatments for MS-related fatigue and a new proposal.

Psychological treatments of MS-related fatigue mostly depend on energy conservation programs. We argue that the evidence for energy conservation training is weak - in contrast to some reviews on this topic. The reasons for our concerns are the use of informed passive control groups allowing negative placebo effects, the lack of predefined primary outcome parameter, statistically rather than clinically significant effects, and the use of insensitive fatigue questionnaires. We propose to base psychological interventions not on a view of fatigue as a constant loss of mental energy but as a subjective representation ("feeling") of an inflammatory state, which draws away attentional capacity. This conceptualization allows to develop a three-step treatment approach: Getting short-term control on fatigue, extinction to reduce fatigue-related avoidance behavior, and a systematic increase of activities by pacing. Our proposal depends on the techniques, that can interrupt ongoing feelings of fatigue and can serve as a basis for extinction. We propose that Progressive Muscle Relaxation might be such a technique. The advantage of our model is that it shares similarities with well-established treatments for phobias and chronic pain and we discuss the shared set of assumptions. Hopefully, this will help to improve the treatment of fatigue in future.

Is recalibration more important than realignment in prism adaptation training for visuospatial neglect? A randomized controlled trial.

Prism adaptation training (PAT) as a treatment for visuospatial neglect (VSN) involves two components: recalibration and realignment. We conducted a randomized controlled trial with PAT protocols requiring different degrees of recalibration and realignment, by using a single or multi-step protocol and varying visibility of the pointing movement. Twenty-five VSN patients received an alertness treatment without prisms, followed by four PAT protocols, encompassing a multi- or single-step procedure with terminal exposure, a single-step procedure with concurrent exposure, and sham PAT, presented in random order. The primary outcome parameter was the mean response time (RT) to left-sided targets in an endogenous variant of the Posner task, and we also measured the sensorimotor aftereffect. The two protocols without visibility of most of the movement trajectory produced significant aftereffects. The single-step protocol without movement visibility resulted in shorter RTs to left-sided targets. Hence, aftereffects depended on the partial invisibility of the movement. Moreover, only allowing VSN patients to recalibrate several times and direct feedback from the pointing errors had a beneficial effect on non-motor leftward visuospatial attention. We provide preliminary evidence that maximizing the conscious experience of movement errors may be an important component for remediating VSN.Trial registration: German Clinical Trials Register identifier: DRKS00025938.

Monocular eye patching modulates reorienting of covert attention in patients with unilateral middle cerebral artery stroke.

Unilateral brain lesions can lead to impaired contralesional attention and reduced ipsilesional and enhanced contralesional superior colliculus (SC) activity. We aimed to investigate whether modulation of SC activation via monocular eye patching can improve contralesional attention. Twenty left-hemispheric (LH) and 20 right-hemispheric (RH) patients with an acute or subacute middle cerebral artery (MCA) stroke completed an endogenous version of the Posner cueing task twice, while the left or right eye was covered with an eye patch. The LH and RH patients showed significantly slower reactions to contralesional than to ipsilesional stimuli. In addition, the eye patch modulated responses to invalidly but not those to validly cued stimuli. Post hoc analyses could not discriminate whether this effect pertained to a particular target side or eye patch position. However, exploratory analyses indicated that the observed eye patch effect might affect the RH group more than the LH group. As predicted 36 years ago, monocular eye patching modulates visuospatial attention, presumably due to differences in SC activation between the two eye patch conditions. However, this modulation seems too weak and unspecific, and therefore possibly not strong enough to be a treatment option for patients with visuospatial attention impairments.

"Cinderella was attacked by the big bad wolf, but the police saved her": intrusions and confabulations on story recall in Korsakoff's syndrome and alcohol-related cognitive impairments.

BACKGROUND: The relation between confabulations and intrusions in patients with Korsakoff's syndrome (KS) and patients with alcohol-related cognitive impairments (ARCI) remains under debate. This study examines (1) differences in the production of confabulations and intrusions between patients with KS and ARCI, (2) whether an altered fairy tale induces more intrusions, and (3) whether different types of intrusions were significantly related to confabulations. METHODS: Twenty-three patients with KS and twenty-two patients with ARCI recalled three different types of stories: a novel story, a fairy tale, and a modified fairy tale. Different types of intrusions were correlated with confabulation measures. RESULTS: Patients with KS produced more intrusions in the modified fairy tale condition than patients with ARCI, but these were unrelated to confabulations. Only unrelated intrusions were related to provoked confabulations. CONCLUSIONS: The results of this study indicate that researchers and clinicians must be aware that in general, intrusions on memory tests should not be interpreted as confabulations. Especially spontaneous confabulations appear to be something completely different from intrusions on any type of story recall. When measuring confabulations it is crucial to use validated instruments.

Phrenology's frontal sinus problem: An insurmountable obstruction?

Whereas some of Gall's critics were quick to assail his organology as materialistic and fatalistic, others questioned his methods and scientific assumptions, especially his craniological tenets. The idea that the skull does not faithfully reflect the features of small, underlying brain areas was repeatedly brought up in the scientific debates. Critics pointed to the frontal sinuses above the eye orbits as evidence for the interior and exterior plates of the cranium not being in parallel-hence, for several or many phrenological organs being unknowable. This article traces the origins of the frontal sinus arguments and how Gall, Spurzheim, and later phrenologists responded to it. It reveals how the two sides fought and remained divided about the significance of the sinuses throughout the nineteenth century-that is, on whether the frontal sinus "problem" was an insurmountable obstacle or one that was merely an inconvenience.

The quest for objectivity and measurements in phrenology's "bumpy" history.

Phrenology is based on correlating character traits with visible or palpable cranial bumps (or depressions) thought to reflect underlying brain areas differing in size and levels of activity. Franz Joseph Gall, who introduced the doctrine during the 1790s, relied heavily on seeing and feeling skulls when he formulated his theory, as did Johann Spurzheim, who served as his assistant until 1813 and then set forth on his own. But Peter Mark Roget, a British critic of the doctrine, first assailed these methods as too subjective in 1818, and never changed his mind. George Combe, a Scotsman who admired Spurzheim, introduced calipers and other measuring instruments during the 1820s, hoping to make phrenology more like the admired physical sciences. In the United States, the Fowlers also called for more numbers, including measuring distances between the cortical sites above the organs of mind. Nonetheless, phrenologists realized they faced formidable barriers when it came to measuring the physical organs of mind, as opposed to basic skull dimensions. This essay examines the subjectivity that left phrenology open to criticism and shows how some phrenologists tried to overcome it. It also shows how vision and touch remained features of phrenological examinations throughout the numbers-obsessed 19th century. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

History of aphasia: A broad overview.

This chapter gives a broad overview of the description and theorizing of a wide range of language disorders resulting from brain damage, commonly classified under the umbrella term "aphasia." It covers works written in Antiquity up to the 20th century. Moreover, it looks at disturbances in various language modalities such as speech, language comprehension, reading, writing, and sign language. In addition, also forms of the more recently discovered primary progressive aphasia are discussed. Finally, important developments in the history of assessment and rehabilitation of language disorders are described. To properly characterize disorders of language, these developments are discussed from the perspectives of neurology, psychology, and linguistics.

Can biofeedback-based training alleviate fatigue and vigilance performance in fatigued MS patients?

MS related fatigue might be related to autonomous nervous system (ANS) dysfunctions or to inflammation related vagal (hyper-) activation. Consequently, influencing ANS status may lead to relieve of fatigue. We used two opposite biofeedback interventions to either increase sympathetic ("self-alert training", SAT) or parasympathetic activation ("progressive muscle relaxation", PMR). We recorded fatigue status of patients before and after a challenging vigilance task, their behavioural performance on this task, their skin conductance response (SCR), and parameters indicating parasympathetic activity concerning heart rate variability (HRV). We repeated these recordings after the biofeedback training sessions. Patients of the SAT group were able to learn to increase their SCR voluntarily. Patients of the PMR group showed increasing parameters indicating parasympathetic modulation of the HRV. The vigilance task increased their feeling of fatigue. However, there was no effect of biofeedback training on either fatigue status or performance on the vigilance task. Our results show that MS patients can learn to change voluntarily their ANS activity using biofeedback instructions based on SCR and this can be used in future studies to test the postulated link between ANS and fatigue. However, in this experimental intervention we were unable to document a relation between ANS activity and fatigue.Trial registration: ClinicalTrials.gov identifier: NCT03268187.

Franz Joseph Gall on God and religion: "Dieu et Cerveau, rien que Dieu et cerveau!"

Franz Joseph Gall's (1758-1828) doctrine of many faculties of mind with corresponding cortical organs led him to be accused of materialism, fatalism, and even atheism. Yet little has been written about the specific charges he felt forced to respond to in Vienna, while visiting the German States, or in Paris, where he published his books. This article examines these accusations and Gall's responses. It also looks at what Gall wrote about a cortical faculty for God and religion and seeing intelligent design in the functional organization of the brain. Additionally, it presents what can be gleaned about his private thoughts on God and organized religion. We conclude that Gall was sincere in his admiration for and belief in God the Creator, but that as an enlightened scientist was recognizing the need to separate metaphysics from the laws of nature when presenting his new science of man.

The Effects of Continuous vs. Intermittent Prism Adaptation Protocols for Treating Visuospatial Neglect: A Randomized Controlled Trial.

Visuospatial neglect may interfere with activities of daily living (ADL). Prism adaptation (PA) is one treatment option and may involve two components: recalibration (more strategic) and realignment (more implicit). We examined whether recalibration or realignment is the driving force in neglect rehabilitation using PA. In a randomized controlled trial with two recruitment series and a cross-over design, 24 neglect patients were allocated to a continuous (PA-c) or intermittent (PA-i) PA procedure. During the PA-c condition, goggles were worn without doffing. In the PA-i condition, patients donned goggles twice (first series of patients) or three times (second series) during training to induce more recalibrations. Primary outcome parameters were performance (omissions) on the Apples Cancellation Test and ADL scores. To assess the efficacy of the PA treatment, we compared effect sizes of the current study with those from three groups from previous studies at the same rehabilitation unit: (1) a passive treatment with a similar intensity, (2) a placebo treatment with a similar intensity, and (3) a PA treatment with fewer therapy sessions. Treatment conditions did not significantly predict scores on primary and most secondary outcome parameters. However, the spontaneous ipsilesional body orientation improved only in patients receiving the PA-i condition and this improvement also appeared in patients showing a strong after-effect (irrespective of condition). Effect sizes for the Apples Cancellation Test and the Functional Independence Measure were larger for both PA treatment protocols than the historical control groups. We conclude that more recalibrations during an intermittent PA treatment may have a beneficial effect on spontaneous body orientation but not on other aspects of neglect or on ADL performance. Clinical Trial Registration: German Clinical Trials Register, identifier: DRKS00018813, DRKS00021539.

Hildegard of Bingen (c. 1098-1179) on sleep and dreams in her Causae et curae and Physica: a historical perspective.

Saint Hildegard of Bingen (c. 1098-1179) was a 12th century Benedictine abbess, a visionary, a composer, a poet, a healer, and one of few medieval women who produced treatises on medicine. In her medical writings, Causae et curae and Physica, the abbess described, among other topics, physical functions and mechanisms of sleep, dreams and waking, emphasizing the importance of sleep for the human body. She regarded sleep as both a passive and an active process. Hildegard warned her readers about sleeping too little or too much, evaluated possible causes of insomnia and nightmares, and discussed potential treatments for these sleep disorders. In this paper, we analyze Hildegard's writings in the context of Greco-Roman physiological theories, which were held to the end of the Middle Ages and later. We also discuss questions concerning the abbess's putative education, the originality of her works, and the significance of her writings in the context of current knowledge on sleep medicine.

Audiospatial evoked potentials for the assessment of spatial attention deficits in patients with severe cerebrovascular accidents.

INTRODUCTION: Neuropsychological assessment of spatial orientation in post-acute patients with large brain lesions is often limited due to additional cognitive disorders like aphasia, apraxia, or reduced responsiveness. METHODS: To cope with these limitations, we developed a paradigm using passive audiospatial event-related potentials (pAERPs): Participants were requested to merely listen over headphones to horizontally moving tones followed by a short tone ("target"), presented either on the side to which the cue moved or on the opposite side. Two runs of 120 trials were presented and we registered AERPs with two electrodes, mounted at C3 and C4. Nine sub-acute patients with large left hemisphere (LH) or right hemisphere (RH) lesions and nine controls participated. RESULTS: Patients had no problems completing the assessment. RH patients showed a reduced N100 for left-sided targets in all conditions. LH patients showed a diminished N100 for invalid trials and contralesional targets. CONCLUSION: Measuring AERPs for moving auditory cues and with two electrodes allows investigating spatial attentional deficits in patients with large RH and LH lesions, who are often unable to perform clinical tests. Our procedure can be implemented easily in an acute and rehabilitation setting and might enable investigating spatial attentional processes even in patients with minimal conscious awareness.

Repeated application of the covert shift of attention task improves endogenous but not exogenous attention in patients with unilateral visuospatial inattention.

BACKGROUND: Most neglect treatment studies focus on automatic re-orientation procedures, assuming a deficit in automatic processes. We compare an automatic- and a controlled procedure, using the endogenous and exogenous variants of Posner's covert shift of attention task. METHOD: In two experiments, neglect patients and patients with a right hemispherical stroke without neglect performed three blocks of Posner's covert shift of attention task (Posner Task) on two days. In Study 1 we used endogenous cues, in Study 2, exogenous cues. RESULTS: In the endogenous task, neglect patients improved significantly with valid left-sided cues between block 1 and 2 on Day 1, subsequently showing a plateauing. They also showed a gradual improvement on invalid trials on both days. In the exogenous condition, all participants responded only increasingly faster on trials with a long stimulus onset asynchrony. Practicing on both tasks led to fewer omissions for left-sided targets, minimally in the exogenous and clearly in the endogenous condition. CONCLUSION: In line with prior neuroanatomical studies, our study shows that practicing an endogenous, but not an exogenous, visuospatial attention task leads to significant improvements in neglect patients, especially for invalid trials, suggesting that neglect treatments based on top-down strategies should be given more attention.

Franz Joseph Gall on the "deaf and dumb" and the complexities of mind.

Franz Joseph Gall used a broad variety of phenomena in support of his organology. Well known are his observations on anatomical features of the brain, species-specific behavioral patterns, the observation that some individuals may excel in one faculty while being mediocre in others, changes in the organs with development and aging, and how the organs associated with the faculties might be affected by diseases and acute brain lesions. We here present a widely overlooked source: his observations on individuals then classified as "deaf and dumb." We discuss how these observations were presented by Gall in support of his organology and in his disputes with empiricists and sensationalists about the nature of mind.

Stephanus Bisius (1724-1790) on mania and melancholy, and the disorder called plica polonica.

Stephanus Bisius (1724-1790) was a physician of Italian descent and a graduate of the University of Pavia. He was invited to the Polish-Lithuanian Commonwealth in the early 1760s and became head of the Faculty of Medicine at Vilnius University in 1781. In 1772, Bisius had authored the first original study on nervous and mental diseases in the Grand Duchy of Lithuania. In his 35-page booklet, written in Latin and Polish, Bisius characterized mania and melancholy as diseases of the brain, explaining that the organs that feed the human soul are affected, not the soul itself. He introduced the principles of humoralism and solidism to readers, and recognized that autopsies had failed to reveal reliable findings concerning mania or melancholy. Bisius also described the origins of the challenging disorder called plica polonica, a strange condition associated with tufts of matted hair. As a physician during the medical Enlightenment, Bisius criticized metaphysical speculations in medicine and stated that plica was only a result of superstitions. Even though he proposed antiphlogistic treatments for patients with mania and melancholy, he maintained that time and faith in God might help some patients overcome their infirmities.

Relation between cognitive fatigue and circadian or stress related cortisol levels in MS patients.

Background Cortisol levels are increased in MS patients. However, the relation between cortisol, cognitive fatigue and load is still unknown and is investigated in this study. METHOD: In 40 MS patients and 20 healthy controls, cortisol levels were assessed (in saliva) in the morning and afternoon, before and after 5 runs of a cognitively demanding divided attention task (lasting in total 25-minutes). MS patients were divided in those suffering from cognitive fatigue (MS-F) or not (MS-NF). RESULTS: MS-NF patients showed elevated cortisol levels in the morning and in the afternoon before the reaction time task compared to healthy controls. Differences in cortisol levels among the four measurements were also larger compared to healthy controls and MS-F patients. These differences could not be explained by medication, EDSS score, MS course, age or gender. MS-NF patients also produced more omissions on the attention task compared to healthy controls and MS-F patients. MS-F patients experienced more fatigue after the attention task, but they did not show a task related performance decline. CONCLUSION: MS-NF patients, and not MS-F patients, deviate in cortisol release and task performance from healthy controls and from MS-F patients. We suggest that MS-NF patients suffer from a dysregulation of their circadian cortisol level.